Sun Ginseng And Anti-cancer Drugs Synergistically Induced Apoptosis In Hela Cells

Cancer is a leading cause of death worldwide. Chemotherapy is one of the most widelyemployed treatments for cancer. However many chemotherapeutic drugs can produceunpleasant side effects, especially when taken in high doses. Combination therapy with twoor more agents can reduce dose and toxicity for a better therapy effect. Therefore in thisthesis, we studied the effect of drugs combination for cancer therapy and the mechanism forit.Epirubicin, a kind of anthracycline drugs, is mainly used for the treatment of cervicalcancer, breast cancer, lung cancer (especially small cell lung cancer) and malignantlymphoma. It forms a complex with DNA by intercalation between base pairs, resulting ininhibition of DNA and RNA synthesis. Intercalation also triggers DNA cleavage bytopoisomerase II, resulting in cytocidal activity, which eventurally lead cell to death. Butepirubicin can also affect normal, healthy cells, particularly those that multiply quickly,such as blood cells, which limits its application to a certain estent. So epirubicin is usuallyused in combination with other medications to treat cancer.Paclitaxel, a diterpenoid pseudoalkaloid, is currently used in the treatment of patients withovarian, breast carcinoma, lung cancer, colorectal cancer, melanoma, head and neck camcer,lymphoma, bladder cancer, prostate cancer and stomach cancer. Paclitaxel is a mitoticmicrotubule inhibitor. It can stabilize the microtubule polymer and protect it fromdisassembly. Consequently, the cells become arrested by the spindle and then die eventuallyby an apoptotic pathway, called mitotic catastrophe phase. Although paclitaxel is a kind ofthe broadest-spectrum anticancer agents, it can lead to hypersensitivity reactions,neutropenia, neurotoxicity, cardiac rhythm disorder and other miscellaneous toxic effects,which seriously worsens the quality of life of cancer patients and results in dosage reductionand discontinuation of treatment.Sun ginseng, a mixed extract of ginseng, contains different types of ginsenodides, especially the polar ginsenosides of Rg3, Rg5and Rk1. It has been reported that sun ginsengcan induce apoptosis in many kinds of cancer. In this thesis, we hypothesize the combinationof sun ginseng and Epirubicin, the combination of sun ginseng and Paclitaxel may causesynergistic effect to overcome cancer chemotherapeutic resistance.In this thesis we draw some conclusions as follows:1. Sun ginseng and Epirubicin, sun ginseng and Paclitaxel respectively actsynergistically to induce apoptotic cell death in human cervical cancer cell HeLa,human colon cancer cell SW111C and highly metastatic colon cancer cell SW480.2. We selected HeLa cell to carry out further study. Our results showed the cytotoxicityleading HeLa cell to death is due to the drugs synergism induced apoptosis.3. Sun ginseng and Epirubicin, sun ginseng and Paclitaxel induced synergistic apoptsisin HeLa cell involves the participation of mtochaondria pathway, but not deathreceptor-mediated pathway. Drugs synergism lead the translocation of Bak and Baxto mitochondria, which enhanced the release of cytochrome c from mitochondria tothe cytosol. Consequently, Caspase-9was activated and then a series of Caspases wasactivated, which eventually lead cell to apoptotic death.In this thesis we proposed a new therapeutic strategy to overcome the chemoresistanceand provided a novel method for the understanding about the intersection of criticalsignaling pathways in combination therapy.