蛋白激酶C及抑制剂在肺癌耐药中的研究进展

Advances of protein kinase C and its inhibitors in drug resistance of lung cancer

耐药已成为当今肺癌化疗过程中的一大难题，其作用机制至今还不十分清楚。蛋白激酶C（proteinkinaseC，PKC）作为多种信号传导过程中的枢纽，不仅参与细胞信息传递、分泌、细胞分化、增殖，更重要的是参与肿瘤细胞的凋亡和分化。国内外研究表明通过抑制PKC的活性，减少其表达量可以增加细胞内药物的积聚导致胞内有效浓度的上升，从而降低肿瘤细胞耐药率。PKC抑制剂对肿瘤细胞具有明显的诱导分化、增强细胞毒性、促进细胞凋亡的作用。目前已有部分PKC抑制剂进入了临床的Ⅰ／Ⅱ期研究中，并取得了一定的疗效，通过对其作用机制的进一步深入探讨，有望在肺癌耐药的研究中取得更多的突破。

Drug resistance has become a major problem in the chemotherapy of lung cancer. The mechanism is not clear yet. As a hinge in multiple signal transduction processes, protein kinase C （PKC） participates in not only cell signal transduction, secretion, cell differentiation and proliferation, but also apoptosis and differentiation of＇tumor cell. Researches have shown that inhibition of PKC activity and reduction of its expression can increase cellular accumulation of drug, leading to the increase of intraeellular effective concentration, thus reducing the drug resistance of tumor cells. PKC inhibitors significantly induce tumor cell differentiation,increase cytotoxicity,and promote apoptosis. A few of PKC inhibitors have already entered part I /1I clinical study with some therapeutic effect. Under the further study of its mechanism,it is probable to achieve more breakthroughs in drug resistance of lung cancer.