The Anti-lung Cancer Effect And Its Mechanism Of Dihydroartemisinin

Objective:Lung cancer is one of the commonest malignant tumors in the world. Its morbidity and mortality are increasing in most countries. So the prevention of lung cancer has become very urgent in the world. Cancer chemotherapy is limited by the development of drug resistance in tumors and adverse side effects in patients. The search for novel anti-tumor agents that circumvent these limitations has turned to natural sources.The genus Artemisia L. belongs to the family of Compositae. Artemisinin, the key ingredient obtained from Artemisia annua is a sesquiterpene lactone containing an internal peroxide group. Dihydroartemisinin is the methabolite of artemisinin in vivo. Pharmacological studies showed that artemisinin and its derivates have the property of rapid absorption, broad distribution, rapid excretion and little toxicity. They have the pharmacologic functions of anti-malarial, anti-schistosome, anti-fetation and immunoregulation. Recent years, it was found that artemisinin and its derivates also have anti-tumour effects. Their high efficiency, low toxicity and selective anti-tumour effect attracted great attention. Although artemisinin and its derivates can suppress the growth of many kinds of tumor cell and induce apoptosis of different types of tumor cells until now the detailed molecular mechanism of its anti-tumor effect is still unclear.Based on selecting lung cancer cell line which is more sensitive to dihydroartemisinin, we used flow cytometry, laser scanning confocal microscopy, RT-PCR and western blot et al to observe the apoptotic induction effect on lung cancer cell and the signal molecules related to cell growth and apoptosis.Material and methods:We took lung cancer cell Calu-3, SPC-A-1, PC-14 as our research subjects and observed the SPC-A-1cell is the most sensitive among these three cell lines. Based on these, we studied the dihydroartemisinin's effects on lung cancer cell growth circle distribution, apoptotic induction and we also studied the signal transduction molecules and signal pathways in the lung cancer cell apoptosis induced by dihydroartemisinin.Our major foundings:1. Dihydroartemisinin can inhibite the growth of SPC-A-1, Calu-3, PC-14 lung cancer cells and the SPC-A-1 is the most sensitive.2. The growth inhibition effect of DHA in SPC-A-1 is a result of its ability to induce apoptosis.3. Dihydroartemisinin can induce the G2/M phase arrest on SPC-A-1 cells.4. Dihydroartemisinin can induce the increase of [Ca2+]i and the increase of [Ca2+]i was involved in the apoptotic induction and at the upstream of the signal pathway. The increased [Ca2+]i is from the intracellular.5. calpain played anti-apoptotic role in the signal pathways.6. Dihydroartemisinin downregulated the mRNA and protein expression of survivin.7. The downregulation of survivin paticipates the G2/M arrest induced by dihydroartemisinin.Conclusion:Calcium and survivin are involved in the anti-lung cancer cell effect of dihydroartemisinin.Make a short summary, our experiment study the growth inhibiton effect of dihydroartemisinin on lung cnacer cell. We further study the process of apoptosis in lung cancer cell induced by dihydroartemisinin and explored the molecule mechanism of its effect. We provide important data for increasing efficiency of anti tumor drug and reducing the drug toxicity.