N(4-hydroxycarbophenyl) retinamide (RII) is a new synthetic analog of retinoids with low toxicity. Its effect on the biological properties associated with tumor malignant behavior of human nasopharyngeal carcinoma cell lines (HNCs), including CNE-2Z parent cell lines and their variants L2, H2, L4 was studied. RII (10(-5) mol/L) caused detectable morphologic differentiation of HNCs. It inhibited growth of HNCs in vitro and decreased ability of these cells to penetrate matrigel-coated filters by using a reconstituted basement membrane invasion assay. These results suggested that RII might be a kind of useful anticancer drug.

G9315, a complex extracted from Glycyrrhizae inflata Bat (III), consists of 6 flavonoids with significant antioxidant effects. At 1 mg dose it inhibited the mouse ear edema induced by croton oil, and showed strong anti-promoting effects on two-stage carcinogenesis in mouse skin induced by DMBA plus croton oil. The TPA enhanced 32Pi-incorporation into phospholipid fraction in HeLa cells was inhibited, and the micronuclei in mouse bone marrow cells induced by cytoxan was also depressed.

The effect of calmodulin antagonist trifluoperazine (TFP) on in vitro drug sensitivity of primary cultured lung cancer cells was studied in 28 cases with MTT assay. TFP was found to enhance significantly the anticancer activities of VCR, ADR and VP16 (P < 0.01 or < 0.05). But TFP could not sensitize tumor cells to DDP. TFP may therefore be useful as an adjunct in chemotherapy of lung cancer.

This study was undertaken to determine the mechanism of resistance of a human bladder cancer cell line SCaBER to mitomycin C (MMC). The IC50 value for MMC in SCaBER cells was higher by 2.7 fold by 1-h drug exposure colony formation assay as compared to another bladder cancer cell line J82. NADPH cytochrome P450 reductase and DT-diaphorase activities were significantly lower in SCaBER cells as compared to those of J82 suggesting that relatively resistance of SCaBER cells to MMC may be due to inefficient drug activation. Further support for this conclusion derives from the observation that sensitivities of J82 and SCaBER cells to BMY25282, a MMC analogue with lower quinone reduction potential, were similar. MMC dependent lipid peroxidation (an indicator of oxygen free radical formation) was higher in SCaBER cells than in J82. The activities of anti-oxsidative enzymes GSH peroxidase and catalase did not differ significantly in these cells. These results suggest that resistance of SCaBER cells to MMC may not be due to the reduced free radical formation in these cells. MMC induced DNA interstrand cross-link (ISC) formation was markedly lower in SCaBER cells than in J82. Taken together, these results suggest that SCaBER cell resistance to MMC may be due to the reduced drug activation and ISC formation in these cells.

K562/A02 is a Cell line with multi-drug resistance established in our laboratory bey long term induction with adriamycin. In this paper, reversal of MDR in K562/A02 cell line by tripiperaquine is reported. The cytotoxicity and intracellular concentration of daunorubicin (DNR) in K562/A02 were measured by MTT colorimetric assay and spectrofluorimetry. The results showed that the sensitivity of K562/A02 to DNR was greatly enhanced by tripiperaquine at 10 micrograms/ml, with an 11-fold increase in cytotoxic activity. The intracellular concentration of DNR in K562/A02 was significantly increased after coincubation with 20 mumol/L tripiperaquine for 3 hours. Our results suggest that tripiperaquine might be used in clinical trial to reverse MDR.

We have previously reported that the malignant phenotype of human liver carcinoma cell line BEL-7404 was reversed by antisense EGFR RNA. The aim of this paper is to explore the effects of an oligomer targeted to mRNA for EGFR and growth of BEL-7404 cells. A 21-mer oligodeoxynucleotides (ODNs) complementary to the 5' initiation region of mRNA for EGFR was synthesized and added to medium. The results showed that the growth of BEL-7404 cells was inhibited by ODNs at concentration of 3.2 mumol/L. Inhibition of DNA synthesis of BEL-7404 cells was dose-dependent and reached to 62.1% at 3.2 mumol/L as measured by 3H-thymidine incorporation test. The inhibition of EGFR gene transcription of the cells was up to 10.5% and 14.3% respectively after incubation with ODNs by 5 and 24 hours as measured by densitometric scanning of dot (RNA) blots of EGFR. The EGFR protein (P 170) expression was also found to be blocked by 4 days' antisense oligomer treatment up to 37.4% as measured by densitometric scanning of specific band of Western blot. The oligonucleotide phosphorothioate (S-ODNs) complementary to the same region of the gene was also synthesized and its growth inhibition effects on BEL-7404 cells were compared with those of unmodified oligomers. ODNs attained their highest effect within 30 hours. The proliferation inhibition rate of the cells didn't increase when cells were cultured in serum free medium. In contrast, the S-ODNs induced inhibition reached comparable level after 96 hours treatment as measured by 3H-thymidine uptake and the effect lasted longer, 1 mumol/L S-ODNs showed a little effect on BEL-7404 cells' proliferation. We concluded that the antisense oligomers directed to mRNA for EG-FR could inhibit the BEL-7404 cells growth by blocking the EGFR gene expression in some degree and the phosphorothioate analogues were more stable than the unmodified ODNs in vitro.

Sixty-three cases with stomach cancer were randomized and observed, the results showed that the count of T lymphocytes in chemotherapy combined with Shenmai injection (SMI) group increased, while in control group it decreased, the difference was significant (P < 0.05). The results also indicated that the count of OKT4 cells and the ratio of OKT4/OKT8 decreased after chemotherapy, but in SMI group both parameters increased in advence which were higher in the 4th week after chemotherapy than that before chemotherapy. However, the count of OKT1 cells and the ratio of OKT4/OKT8 were still in low level. Serum interleukin-2 receptor (sIL-2R) level also decreased (P < 0.05), while activities of natural killer cell (NK) and lymphokine activated killer cell (LAK) level increased (P < 0.05) in SMI group. Although the sIL-2R level had no change, both NK and LAK level decreased in control group. In addition, the difference of IgA, IgM, IgG level were not significant between these two groups. This suggested that SMI might improve human immune function to facilitate the chemotherapy of patients with stomach cancer.

Achyranthes bidentata polysaccharides (ABP), extracted from the root of Achyranthes bidentata Blume, 25-100mg.kg-1.d-1 x 7 could inhibit tumor growth by 31%-40%. Combination of cyclophosphamide (Cy) and ABP increased the rate of tumor growth inhibition to 58%. ABP 50 and 100% mg/kg ip could potentiate LAK cell activity and increase the Con A (5 micrograms/ml)-induced production of tumor necrosis factor (TNF-beta) from murine splenocytes. The optimal time for TNF production was on d 8. We also found that ABP 1-2 micrograms/ml strongly inhibited the proliferation of S180 and K562 cells in vitro. The S180 cell membrane content of sialic acid was increased and phospholipid decreased after ABP acting on cells for 24 hours. The changes were significantly different from the control group (P < 0.05 or P < 0.01), but the membrane cholesterol content and membrane mobility indices (Ch/PI) were not affected. The results suggest that the antitumor mechanism of ABP may be related to potentiation of the host immunosurveillance mechanism and the changes in cell membrane features.

To confirm the claims that the procarbazines (PCZ) effect on stem spermatogonia can be overcome by gonadal steroid hormones,mature,LBNF1 male rats were implanted with silastic capsules containing testosterone (T 200 mm) + estradiol (E 50 mm). The silastic capsules of control and TE groups were removed 24 hours after the PCZ injection and the rats were sacrificed 9 weeks later. The functional status of the testis and the hormonal parameters at the time of the injection of PCZ were measured and correlated with the degree of protection ,as measured by the recovery of sperm counts. The results indicated that testosterone and estradiol does protect spermatogenesis from PCZ intoxification. To determine whether the protection is specific for stem spermatogonia, we also measured body weight loss 3-4 days, lymphocyte counts 1 day, and spermatocyte count 9 days after PCZ treatment. There were no differences in the dose response curves of these three assays between the hormone and sham treated rats. The lack of protection indicates that the hormonal protection of stem spermatogonia was not due to the alterations in either systemic or testicular pharmacokinetics of spermatocyte. We conclude that A3 spermatogonia and preleptotene spermatocyte are sensitive to PCZ and there is no evidence of hormonal protection for the differentiated spermatogonia and preleptotene spermatocyte.

The result of the experiment indicated that Kang Ai-bao II ([symbol: see text] II) had a destructive effect on DNA and RNA of cancer cells. Our study provided the basis for the clinical practice. The effect of Kang Ai-bao II on U14 cancer cell in C57 BL mice was investigated with confocal laser scanning microscopy.

The purpose of this study was to determine what proportion of drug resistance of MDR cell variant K562/Dox was attributed to the reduced steady state intracellular drug accumulation related to overexpression of P-glycoprotein. K562/Dox was derived from repeated exposure of human erythroleukaemic cell line K562 cell to doxorubicin. As assessed with MTT assay, the resistance of K562/Dox to 7 cytotoxic drugs increased variably in the range between 1200 and 11 folds. K562/Dox cells were positively stained with anti-human p-glycoprotein monoclonal antibody JSB-1, indicating overexpression of P-gp. Intracellular drug accumulation in K562/Dox, though significantly reduced as compared with that in K562 cells, was maximally restored by concurrent exposure of cells to 6 mumol/L verapamil and 1.72 mumol/L either of the doxorubicin, epirubicin or daunorubicin. Similar results were obtained by exposure of cells to 12 mumol/L verapamil and 8.62 mumol/L drug, indicating that restoration of intracellular drug accumulation in MDR cells was dependent on the relative concentrations of verapamil to drug. However, the resistances of K562/Dox cells to epirubicin and daunorubicin still remained for about 5.6 and > 6.6 folds, respectively, even at verapamil concentration of 6 mumol/L, suggesting at least a relatively big fraction of drug resistance was not directly related to the altered cellular pharmacokinetics associated with overexpression of P-glycoprotein.

The effects of antitumor drugs of croton alkaloids (CA) extracted from croton, and cisplatin on the structure of human erythrocyte membrane and bovine serum albumin (BSA) were studied with the techniques of circular dichroism, fluorescence spectroscopy and ultraviolet absorption. From measuring circular dichroism between 200-240nm, it was found that the alpha helix of membrane and BSA increased after CA addition. Cisplatin was also found effective in altering membrane alpha helical content. BSA showed a loss of fluorescence intensity and a blue-shift of emission peak after CA addition. The florescence quenching and peak shift may reflect the movement of tryptophan to a more nonpolar environment (the hydrophobic portions of proteins). This is consistent with the increase in helicity of BSA in the presence of CA. From measuring fluorescence polarization of membrane, it was found that membrane fluidity decreased in the presence of CA, but did not change in the presence of cisplatin. The results indicate that both CA and cisplatin lead to alterations in the secondary structure of membrane protein. The conformation change in membrane protein may account for the pharmocological effect of CA and cisplatin.

Type I and type II cAMP receptor proteins participate in cell growth regulation, differentiation and neoplastic transformation of neoplasms. In this paper the growth regulatory effects of cAMP analogs, DBcAMP (non-site-selective) and 8-Cl-cAMP (site-selective) on a highly metastatic human lung cancer cell line PG were studied. By MTT assay, DBcAMP at 1mmol/L was found to inhibit PG growth by 30% on the day 8, while 8-CL-cAMP at 10-20 mumol/L inhibited the growth by 75%-80%. When phosphodiesterase inhibitor isobutyl-1-methyl-xanthine (IBMX) was added the inhibitory effect of 8-Cl-cAMP was not enhanced, whereas that of DBcAMP was significantly enhanced. The invasiveness and colony-forming ability of the treated cells decreased. The cAMP level as determined by RIA was much more increased in DBcAMP-treated than in 8-Cl-cAMP-treated PG cells. The result suggests that 8-Cl-cAMP and DBcAMP exert their effects on tumor cell growth and invasion by defferent mechanisms.

Chemosensitivities of 32 human breast cancer to 6 antitumor drugs were assayed in vitro using MTT colorimetric method. The results showed that the chemosensitivity of primary breast cancer cultures varied remarkably from one patient, and from one drug, to another with hundred-to thousand-fold differences. The distribution of 50% inhibition concentration (IC50) was significantly deviated from normal distribution (P < 0.0001), and the drug sensitivity could be divided into four different catagories by means of percentile method. Preliminary results showed that the in vitro chemosensitivities of different antitumor drugs were consistent with the clinical therapeutic responses It seems that the herein reported assay might be useful on an individual basis to optimize chemotherapy of human breast cancer.

Using flow cytometry the authors analysed the effect of 24 Chinese medicinal herbs (CMH) in compound recipe on proliferation index (PI), DNA index, protein index and ratio of various phases in cell cycle of human lung adenocarcinoma cell (SPC-A-1), The PI were more than 20%, in 4 CMH, while 3 CMH such as Gynostemma pentaphyllum, Glehnia littoralis, Panax Ginseng, could strengthen the body resistance. That suggested using CMH of strengthening body resistance not only served as conventional tonice but also as tumor cell inhibitor. Meanwhile the action point of 24 CMH on cell cycle were different. Therefore according to these results a new recombined Chinese recipe would be more effectively used for clinical practice.

We studied DMH induced colon cancer in 120 wistar rats, which were divided into 8 groups based on different diets. They were killed and autopsied on 4 weeks after the last injection of DMH. The tumors in various organs including its characteristics, number, site, histological types and ultrastructural changes were observed. The results showed that high fat diet has a significant effect on DMH induced colon cancer. Selenium and calcium can inhibit the effect of DMH and decrease the incidence of colon cancer. Selenium can also interfere the effect of high fat diet but germanium has no effect on colon carcinogenesis.

Diethyl-dithiocarbamate (DDC) is a compound with wide spectrum of pharmacologic activities. It has been shown to enhance the tumor cytotoxic effect of Pingyangmycin (PYM). In this paper, the effect of DDC on the distribution of 99mTc-labeled PYM in mice bearing subcutaneous transplant of Ehrlich carcinoma is reported. The results indicate that DDC did not affect the absolute concentration of PYM in the tumor but it accelerated its excretion in the urine and decreased the concentration of PYM in the non-tumorous tissues. Therefore, DDC could help alleviate the damaging effect of PYM on normal tissues without affecting its tumor cytotoxic activity.