AIM　To study the apoptosis-inducing and growth-inhibitory effect of rhein, an herb-derived compound, and its combination with mitomycin C (MMC) on cultured tumor cells. METHODS　MTT assays were used to determine the inhibition of proliferation by drugs in several tumor cell lines. Nucleoside transport and DNA synthesis inhibition were determined by ［3H］ thymidine transport and incorporation assays. Flow cytometry, electrophoresis on agarose gels and morphological assesment were applied to analyze the apoptotic changes. RESULTS　The IC50 values of nucleoside transport was 19.1 μg*mL-1 and that of the DNA synthesis inhibited by rhein was 27.4 μg*mL-1. In MTT assay the IC50 values of rhein for KB, hepatoma BEL-7402 and mammary carcinoma MCF-7 cells were 11.5 μg*mL-1, 14.0 μg*mL-1 and 18.4 μg*mL-1 respectively. Synergistic effect of rhein and MMC was found in all the three cell lines. As found, rhein induced apoptosis in KB cells, and the increase of apoptotic cells reached 71.0% at 96 h. The combination of rhein and MMC enhanced the induction of apoptosis significantly. CONCLUSION　These results suggest that rhein, as a biochemical modulator, might be potentially useful in cancer chemotherapy.

Tea polyphenols (TPs), major biological active constituents of green tea, exert moderate and selective anticancer effects. Molecular mechanisms of TPs in cancer prevention and treatment involve multiple potential molecular targets. TPs inhibit growth factor receptor-mediated signal transduction pathway, decrease the activities of mitogen activated protein kinases and activator protein transcription factor-1, block nuclear factor-kappaB signaling pathway, reduce proteasome activity, lower overexpression of COX-2, subside dihydrofolate reductase and telomerase, and inhibit DNA methylation and matrix metalloproteinases. Furthermore, TPs enhance the inhibitory effect on the growth of cancers by traditional anticancer drugs or targeted antitumor drugs in vitro and in vivo and reverse multidrug resistances of cancer cells to vincristine, doxorubicin, and 5-fluorouracil. Besides, TPs reduce the nephrotoxicity induced by cisplatin, ameliorate irinotecan-induced side effects in the small intestine of mice, and decrease bleomycin-caused DNA damage in human leukocytes. TPs also increase antitumor activity of vaccine through immunological modulation. TPs play roles of the augmentation of antitumor effects, the reversal of multidrug resistance, and the reduction of side effects of chemotherapeutic drugs. TPs could be used as biochemical modulators in cancer therapy.

Aim To study the mechanism of inhibition of basic fibroblast growth factor (bFGF) related signal transduction by lidamycin in cancer cells. Methods MTT assay was used to determine the growth inhibitory effect of lidamycin (LDM) and adriamycin (ADR) in several cancer cell lines. The inhibition of bFGF bound to its receptor by LDM was measured with [ 125I ]-bFGF binding assay.Intracellular Ca2+ stimulated by bFGF was measured by Fura-3. The formation of bFGF- receptor immune complex and the inhibitory effect of LDM on the activity of PKC isoenzymes induced by bFGF in cancer cells were identified by Western blotting analysis. Results LDM displayed extremely potent growth inhibitory effect on several cancer cell lines in a dose-dependent manner. A comparison of the IC50 values showed that the effect of LDM was 1 000-fold more potent than that of ADR. LDM blocked the specific by anti-FGFR specific antibody, LDM inhibited the formation of bFGF-receptor immune complex. bFGF demonstrated that LDM inhibited the activity of PKC isoenzymes in cancer cells stimulated with bFGF.Conclusion The blocking of bFGF receptors in the signal transduction pathway may be involved in the effect of LDM on cancer cells.

The use of monoclonal antibodies (mAbs) for cancer therapy has achieved considerable success in recent years. Approximate 17 monoclonal antibodies have been approved as cancer therapeutics since 1997. Antibody-drug conjugates (ADC) are powerful new treatment options for cancer, and naked antibodies have recently achieved remarkable success. The safety and effectiveness of therapeutic mAbs in oncology vary depending on the nature of the target antigen and the mechanisms of tumor cell killing. This review provides a summary of the current state of antibody-based cancer therapy, including the mechanisms of tumor cell killing by antibodies, tumor antigens as antibody targets, clinical effectiveness of antibodies in cancer patients and nanoparticles-based ADCs.

AIM　To investigate the therapeutic effect of boanmycin (BAM, bleomycin A6) on colon carcinoma 26 and its hepatic metastasis in mice. METHODS　A series of models including subcutaneous transplantation, orthotopic transplantation in cecum subserosa, intra-hepatic transplantation of tumor, and intra-splenic transplantation of tumor accompanied with hepatic metastases were employed. In addition, LEICA Q 500IW image analysis system was used to determine the area of metastatic lesions in the liver in histopathological sections. RESULTS　BAM at 5 mg*kg-1 and 2.5 mg*kg-1 inhibited the growth of subcutaneous tumors by 78.7% and 61.9%, and the orthotopic tumors by 99.4% and 90.0%; and the intra-hepatic tumors by 86.9% and 75.7%, respectively. Determined by the numbers of metastatic nodules, BAM at 10 mg*kg-1 and 5 mg*kg-1 inhibited hepatic metastases from intra-splenic transplantation by 97.6% and 56.8%; and evaluated by image analysis of metastatic lesions, by 100% and 63.3%, respectively. CONCLUSION　Boanmycin is highly effective in a panel of models including the subcutaneous, orthotopic, intra-hepatic transplanted tumors, and hepatic metastases of murine colon carcinoma 26.

C1027, an anticancer antibiotic, showed extremely potent cytotoxicity against cultured cancer cells, being over 10,000-fold more potent than adriamycin. C1027 acted rapidly; DNA synthesis of hepatoma cells was suppressed within 10 mintus of exposure. C1027 consists of two moieties, a new enediyne chromophore and an apoprotein; the chromophore serves as the active part of the molecule. C1027 molecule can be dissociated and reconstituted. The reconstituted C1027 was as potent as natural C1027. Through a newly developed method, enriched conjugation C1027 was conjugated to monoclonal antibodies. As determined by clonogenic assay, the conjugates displayed highly-potent, specific cytotoxicity to target cancer cells. The conjugates exerted marked therapeutic effects against hepatoma and gastric cancer xenografts in nude mice; at tolerable dose, tumor inhibition rate reached 85% (P

Objective To explore the effect of recombinant scFv (3G11)directed against type IV collagenase in combination with cisplatin on the therapy of hepatocellular carcinoma.Methods The effects of cisplatin on the type IV collagenase secreted by cancer cells were investigated by gelatin zymography analysis and Western-blot.The antitumor activity of scFv (3G11)in combination with cisplatin was evaluated by MTT assay in vitro and a mouse hepatoma 22 model in vivo.Results Cisplatin inhibited the activity of type IV collagenase.ScFv (3G11)in combination with cisplatin showed significant inhibition effects on the growth of hepatocellular carcinoma both in vitro and in vivo.The coefficient of drug interaction(CDI)was less than 1.Conclusions ScFv (3G11)in combination with cisplatin demonstrated synergetic effects on the therapy of hepatocellular carcinoma.

This study is to investigate the effects of ubenimex on tumor cell invasion and apoptosis, dose relationship and mechanism. Immunofluorescence staining was performed to detect the expression of CD13 in HT-1080 cells. MTT assay was used to analyze the effect of ubenimex on cell proliferation. Annexin V-EGFP/PI was used to detect apoptotic cells by flow cytometry. Cell cycle was analyzed using flow cytometry. Ala-pNA was used as substrate to evaluate the effect of ubenimex on the aminopeptidase activity. Transwell assay was used to analyze the effect of ubenimex on cell invasion and migration ability. Western blotting was used to detect the expression level of CD13. MMP activity was analyzed using gelatin zymography. The results showed that ubenimex at high concentration inhibited the proliferation of HT-1080 cells (IC50: 3.8 mg x mL(-1)), and induced cell apoptosis. Cell cycle was blocked at G1 phase. Ubenimex at low concentration inhibited the aminopeptidase activity of HT-1080 cells (IC50: 8.3 microg x mL(-1)) and inhibited cell invasion, but it had no effects on the cell migration and proliferation. Ubenimex had no effects on CD13 expression and MMP activity. In conclusion, ubenimex at low concentration can inhibit the invasion ability of tumor cells by directly inhibiting the aminopeptidase activity; ubenimex at high concentration can inhibit the proliferation of tumor cells and induce cell apoptosis by a CD13-independent pathway.

In the present study, a new compound named 17-(6-cinnamamido-hexylamino-)-17-demethoxygeldanamycin (CDG) was obtained by introducing the cinnamic acid (CA) group into the 17-site of geldanamycin (GDM). The anti-cancer effects of CDG in vitro and in vivo were evaluated. MTT assay was used to examine the inhibitory effect of CDG on the proliferation of MCF-7, HepG2, H460 and SW1990 cells. Immunofluorescent staining flow cytometry combined with Annexin V-FITC/PI staining were used to detect apoptotic cells. Transwell assay was used to analyze the effect of CDG on cell invasion and migration ability. Western blotting was used to detect the expression levels of RAF-1, EGFR, AKT, CDK4 and HER-2 of MCF-7, HepG2 and H460 cells. The toxicities of CDG and GDM were evaluated in mice. Using the subcutaneously transplanted MCF-7 xenograft in nude mice, inhibitory effect was evaluated in vivo. The results showed that CDG inhibited the proliferation of cancer cells (IC50: 13.6-67.4 microg.mL-1). After exposure to CDG for 48 h, most cells presented typical morphologic changes of apoptosis such as chromatin condensation or shrunken nucleus. The rates of apoptosis of MCF-7, HepG2, H460 and SW1990 cells incubated with 10 microg.mL-1 CDG were 23.16%, 27.55%, 22.21%, 20.47%, respectively. A dose-dependent reduction of migration of four cell lines was found after exposure to CDG. The decreased levels of RAF-1, EGFR, AKT, CDK4 and HER-2 showed that CDG possessed HSP90 inhibitory effect. The result of animal toxicity test on the mice suggested that CDG had lower toxicity than GDM. Meanwhile, CDG inhibited the growth of MCF-7 xenografts of athymic mice.

This study is to investigate inhibitory effects of lidamycin (LDM) on the proliferation of HERG K+ channel highly expressing cancer cells and its synergy with anticancer drugs. MTT assay was used to examine the inhibitory effects of lidamycin combined with various anticancer drugs on the proliferation of human lung cancer A549 cells, human colon cancer HT-29 cells and herg-stably-transfected A549 cells. Using the xenograft model of subcutaneously transplanted HT-29 in nude mice, inhibitory effect was appraised in vivo. The coefficient of drug interaction (CDI) was used to evaluate the synergistic effect of drug combination. LDM significantly inhibited the proliferation ofA549 cells and HT-29 cells with IC50 values of 2.14 and 4.64 ng mL(-1), respectively. The efficacy in HT-29 cells with high HERG potassium expression level is less potent than that in A549 cells with low expression level. In terms of IC50 values, LDM suppressed the growth of herg-stably-transfected A549 cells less potently than pCDNA3.1-stably-transfected A549 cells. There existed synergistic effects in the combinations of fluorouracil (5-FU) and LDM, doxorubicin (DOX) and LDM, or hydroxycamptothecine (HCPT) and LDM. CDI values of the combinations of 5-FU and LDM were more than 0.75. CDI values of LDM and DOX were more than 0.70, but some CDI values of LDM and HCPT were less than 0.70. As for the CDI values, synergistic effects of the combination of LDM and HCPT were the most potent of the three groups. There is no relationship between the inhibitory effect of the growth of cancer cells by 5-FU and HERG potassium expression level. HERG expression level negatively correlated with inhibitory effect on the proliferation of cancer cells by DOX. HERG expression levels and chemosensitivity were positively correlated for HCPT. In the model of subcutaneously xenograft transplanted HT-29 in vivo, LDM and/or HCPT effectively inhibited the growth of HT-29 in nude mice, and the optimum CDI of the combination of LDM and HCPT was less than 1. HERG expression level negatively correlates the chemosensitivity of cancer cells to LDM. There exist synergistic effects in vitro and in vivo in the combination of LDM and HCPT, which inhibitory effects of the proliferation of cancer cells positively modulated by HERG potassium expression level. HERG K+ channel may become a target of combined therapy for choosing anticancer drugs.