肝癌在我国发病率很高,而且是致死率第二高的恶性肿瘤。sorafenib作为被FDA批准的肝癌临床靶向药物，尽管在临床上提高了患者的生存期，但肿瘤的药物响应率普遍较差，因此阐明肝癌细胞对sorafenib的耐药机制是极其重要的。过去的研究表明代谢重编程与肿瘤耐药密切相关。然而，肝癌中代谢重编程所介导的sorafenib耐药机制还不清楚。我们的前期结果表明sorafenib激活了前列腺素合成途径，并促进了肝癌细胞中脂滴的形成。抑制前列腺素的合成可以显著减少脂滴的形成，降低活细胞数并诱导凋亡。据此我们提出假设，前列腺素的生物合成通过调控脂滴自噬来促进肝癌对sorafenib的耐药。该研究中我们拟研究前列素合成在sorafenib药物响应过程中的作用，阐明抑制前列腺素合成是否可以克服肝癌细胞对sorafenib的获得性耐药。本研究提示了在肝癌中靶向前列腺素合成来治疗肝癌的潜在临床价值。

Hepatocellular Carcinoma (HCC) is prevalent and causing second highest fatality rate in China. Although sorafenib, the drug approved by FDA for HCC treatment, improved overall survival of HCC patients, the tumor response is generally quite low. Therefore, it is crucial to understand the mechanism of sorafenib resistance in HCC patients. Previous study showed that metabolic reprogramming contributes to chemoresistance in human cancers. However, the role of metabolic reprogramming in mediating sorafenib resistance in HCC is still not understood yet. We recently found that sorafenib activates prostaglandin biosynthesis, resulting in increase of lipid droplets(LDs) formation. Inhibition of prostaglandin synthesis significantly attenuates sorafenib- induced LDs formation and decreases cell viability by inducing apoptosis in HCC. Herein, we hypothesize that prostaglandin biosynthesis confers sorafenib resistance through facilitating lipophagy. In this study, we propose to investigate the role of prostaglandin biosynthesis in regulating LDs formation in response to sorafenib, aiming to determine if disruption of prostaglandin production can overcome acquired sorafenib resistance in HCC cells. This study suggests that prostaglandin biosynthesis may be of great therapeutic value for HCC treatment.