理冲生髓饮有效组分调控PI3K/AKT信号通路逆转卵巢癌干细胞耐药的实验研究

卵巢癌干细胞是卵巢癌生长分化，耐药和复发的根源。具有类似干细胞的自我更新和增殖能力，能够逃避或抵抗化疗药物的毒性作用。研究表明PI3K/Akt信号通路表达的变化可促进细胞增殖、抑制凋亡、提高癌细胞对化疗药物的耐受性，上调HIF-1α的转录活性维持肿瘤细胞的增殖和干细胞特性。PTEN可调控PI3K/Akt的活性。课题组既往研究证实中药复方理冲生髓饮（LCSSY）能够促进卵巢癌细胞凋亡，其机制与下调HIF-α及上调PTEN等表达，诱导细胞凋亡、减少细胞黏附有关。 因此本实验以PI3K/AKT为作用靶点，中药复方抑制卵巢癌干细胞增殖，逆转化疗耐药为新思路。为进一步明确LCSSY是否通过PI3K/AKT通路减少卵巢癌干细胞增殖、逆转化疗耐药的作用，本课题以人卵巢癌细胞株分离卵巢癌干细胞，从体内外水平探讨LCSSY对信号通路中相关蛋白和基因表达的调控，探讨LCSSY对卵巢癌干细胞的作用及逆转耐药机制

Ovarian cancer stem cells are the main cause of the ovarian cancer growth and differentiation,drug resistance and relapse.As so as stem cells they have ability of self-renewal and proliferation to resist the escape of toxic effects of chemotherapy drugs.Studies have shown that changes in the expression of PI3K/AKT signaling pathway can promote cell proliferation,inhibition of apoptosis of cancer cells to improve chemotherapy tolerance and upregulate HIF-αtranscrpional activity to maintain the proliferation of tumor cells and characteristics of stem cells.PTEN can regulate the PI3K/AKT singnaling pathway.Previous strdies of our research group have comfirmed that LCSSY can promote apoptosis in ovarian cancer.Its mechanism have relation with down HIF-αand regulating PTEN's expression and etc to induce apoptosis and reduce cell adhesion. Therefore,this experiment takes PI3K/AKT as target,chinese herbal compound inhibite ovarian cancer stem cells and reverse chemotherapy resistance as the new ideas.To further clarify whether LCSSY is to reduce ovarian cancer stem cells proliferation to reverse mechanism of resistance to chemotherapy through PI3K/AKT pathway.This topic isolates ovarian caner stem cells form human ovarian cancer and discusses the regulation of LCSSY in relating proteins and gene expression levels of signaling pathways from vitro and vivo.Discuss the role of LCSSY in ovarian cancer stem cells and reversing resistance mechanisms.