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 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.

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.

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.

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

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.

This study is to optimize the preparation process of fusion protein Fv-LDP which was expressed in the form of inclusion body and consisted of lidamycin apoprotein LDP and single-chain Fv antibody (scFv) directed against type IV collagenase. The preparation and the dissolution of inclusion body, the immobilized metal affinity chromatography of the target protein and the renaturization by stepwise dialysis were optimized by single-factor analysis or orthogonal design. In addition, the refolded fusion protein Fv-LDP was refined by Sephadex G-75 chromatography followed by fluorescence-activated cell sorter (FACS)-based saturation binding assay to measure its antigen-binding activity. After optimization of the process, the purity of fusion protein Fv-LDP existed in the inclusion body was 63.9% and the corresponding solubility was 95.7%; Under denaturing conditions, the purity of fusion protein Fv-LDP was more than 95% after the purification process. The percentage of monomeric fusion protein Fv-LDP was 60% after the refolding process, while it was further refined to 85% which was 5.6-fold higher than that of the initial refolding condition. The refined fusion protein Fv-LDP could bind to human lung adenocarcinoma PAa cells and human hepatoma BEL-7402 cells with the dissociation constants (Kd) of 0.176 micromol x L(-1) and 0.904 micromol x L(-1), respectively. The preparation process of fusion protein Fv-LDP has been successfully optimized, which provides the experimental basis for the production and future development of fusion protein Fv-LDP, and might serve as a relatively practical system for the preparation of other scFv-based proteins expressed in the form of inclusion body.

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 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.