Experimental Studies On Anticancer Effect Of Luteolin Combined With Cisplatin

[Background and objective] Tumor is one of the diseases threating human life and health, and the incidence of the disease is increaing year after year. As the latest statistics shown, the age of cancers trends to be younger. Chemotherapy, one of the three major means in cancer treatment, has irreplaceable role in cancer treatment. Multidrug resistance (MDR) of cancer cells is a major cause of failure in chemotherapy and the most common and difficult issue in cancer chemotherapy. To find efficient and low toxicity sensitizing agents is an effective strategy to overcome multi-drug resistance and improve the efficacy of chemotherapy drugs.In vivo and vitro experiments and epidemiological investigation indicated that flavonoids play an important role in tumor prevention and treatment. Luteolin, an important flavonoid present in a variety of edible plants, exhibits a wide spectrum of pharmacologic properties. Researches confirmed that luteolin can significantly inhibit many tumor cells growth and proliferation, which has a potential value of clinical application. The mechanism of the anti-cancer effect of luteolin might be related to the induction of cell apoptosis, inhibition of cell proliferation, and influence of cell metabolism. Cisplatin and its derivatives are among one of the most effective anticancer drugs used clinically in the treatment of solid rumors. However, inherent or acquired resistance by tumor cells to cisplatin is one of the major limitations in cisplatin chemotherapy.Induction of cell apoptosis is an important mechanism of anticancer efficacy of many chemotherapy drugs including cisplatin and is expected to become the new target and new approach to treat cancer. Many cancers are charcaterized byinactivating mutations in pro-apoptotic protein, for example, in the tumor suppressor p53. Alternatively, anti-apoptotic proteins such as BCL-2 and IAP family members are frequently upregulated. This cancer-cell-specific aberrations enable evasion of apoptosis and also confer resistance to chemotherapeutics that tipically by induction of apoptosis. The best way forward seems the combined treatment of cancer cells with therapeutics that are designed to exploit several cancer related aberrations. Targeted therapies that are designed to induce apoptosis in cancer cells selectively are currently the most promising anti-cancer stratagies.The purpose of this study was to evaluate the effect of luteolin combined with anticancer drug cisplatin on the apoptosis and cell cycle of human lung adenocarcinoma cell A549, human breast carcinoma MCF-7 and human cervical cancer cells HeLa and to find out the molecular mechanisms of the sensitization effect of luteolin on cancer cell killing induced by cisplatin. So we can further provide experimental evidence to support luteolin's potential clinical application as a chemosensitizer in cancer therapy.[Methods] The cell survival rate of HeLa cells treated with luteolin and cisplatin at different concentrations and time points was measured by MTT assay. AO/EB (read in fluorescence microscopy) and flow cytometry are used to detect the effect of luteolin combined with cisplatin on the apoptosis of A549 MCF-7 and HeLa cells. And cell cycle of these cells was analyzed by flow cytometry. The expression of p53 in tumors cells was detected by western bloting. All of the experiment results were analyzed by software SPSS 13.0 and Quantity One and p<0.05 is statistically significant. [Results] The result from MTT assay shows that both luteolin and cisplatin of different concentration inhibit proliferation in a dose- and time-dependent manner. The apoptotic rate of was A549 and HeLa cells significantly raised by combination of luteolin and cisplatin, which showed a relationship with cell cycle arrest. And the type of cycle arrest varies according to different cells. However, combination of luteolinand cisplatin only lead to MCF-7 cells minor apoptosis and luteolin can enhance cisplatin effect of cell cycle arrest on MCF-7 cells. Combination of luteolin and cisplatin can significantly scavenge intracelluar ROS. As the data from western blotting shown, combination of luteolin and cisplatin could signaficantly elevate p53 protein level. [Conclussion]1. luteolin combined with cisplatin can significantly induce apoptosis of human lung adenocarcinoma cells A549, and Hela cells in a synergistic way;2. Luteolin combined with cisplatin can induce cell cycle arrest of A549, Hela and MCF-7 cells;3. p53 may involve in the regulation of luteolin and cisplatin-induced apoptosis.