铂类药物耐受依然是肿瘤临床治疗中的瓶颈问题。在国家自然基金等资助下，我们发现顺铂通过自噬、内质网应激等适应性反应，干扰Bcl-2家族蛋白间相互作用引起卵巢癌顺铂耐药。但是，仅从这些机制来解释Bcl-2等的变化是不全面的，可能还存在更加复杂的机制。我们的前期工作提示，线粒体生物合成转录辅激活因子PGC1α及其相关转录因子可能与卵巢癌顺铂耐药密切相关。我们推测，PGC1α转录激活复合物发挥整合线粒体生物合成的核转录模式，使线粒体与细胞核间形成双向的信号网络系统，进而决定线粒体Bcl-2家族蛋白的定位与功能，最终导致对化疗药物的抵抗。因此，我们拟采用BH3谱分析等技术，在评估卵巢癌顺铂耐药细胞Bcl-2家族蛋白功能的基础上，利用转录因子检测技术，分析PGC1α介导的核转录模式对线粒体数量与功能，以及其对线粒体Bcl-2家族蛋白定位的影响，从细胞核-线粒体-细胞核信号传递角度阐明卵巢癌耐药机制。

Platinum-based chemotherapy resistance is still the obstacle of ovarian cancer clinic treatment. Under the auspices of National Natural Science Foundation of China, we found that cisplatin disturb the interaction between Bcl-2 family members triggering ovarian cancer cisplatin resistance through cellular adaptation, such as autophagy or endoplasmic reticulum stress. However, only from the aspect of cellular adaptation to explain the changes in Bcl-2 is not comprehensive, the mechanism may be more complex. Our previous studies suggested that mitochondrial biogenesis transcriptional coactivator PGC1α and transcription factors (Nrf1, Nrf2 and ERRα) may be involved in ovarian cancer cisplatin resistance. We presume that PGC1α transcriptional activator complex mediated bidirectional mitonuclear communication via integrating the crosstalk between mitochondrial biogenesis and nuclear transcriptional mechanisms determine the traslocation and function of mitochondrial Bcl-2 family proteins, leading the resistance to chemotherapeutic drugs. Thus, we utilize BH3 profiling to evaluate the function of Bcl-2 family proteins in cisplatin-resistance ovarian cancer cells. Investigation the imfact of PGC1α-mediated transcriptional mechanisms in mitochondrial mass and function through transcription factor detection technology to ensure the mitochondrial Bcl -2 family protein localization. This research will elucidate the mechanism of ovarian cancer reversal cisplatin resistance from nuclear-mitochondrion-nuclear signal transduction.