整合式生物資訊分析發現紫檀茂可逆轉肝癌細胞對 Sorafenib 的藥物阻抗

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death worldwide. Sorafenib (NEXAVAR^®), a multikinase inhibitor, has been approved as one of first-line systemic therapies for patients with HCC; however, its efficacy is compromised by the chemoresistance of the tumor cells. Liver cancer cells acquired resistance to Sorafenib by activating Akt signaling, triggering epithelial-mesenchymal transition, modulating autophagy, and increasing antioxidative capacity. Lowered Akt activation has been reported to enhance autophagy and apoptosis in Sorafenib-resistant HCC. Phytochemical Pterostilbene (PS)-suppressed cancer cell growth and tumor progression were observed via inhibiting cell cycle progression and PI3K-Akt signaling as well as triggering apoptosis and autophagy. Here, through analyzing the transcriptomics data of HCC Huh7 and Sorafenib-resistant Huh7 (Huh7R), the resistance of Huh7R was discovered to be associated with cell cycle, DNA repair, and autophagy. The molecular actions of PS were further identified by querying the transcriptomics profiles deposited in the Connectivity Map database. Indeed, PS-enhanced sensitivity in cell growth inhibition of Huh7R to Sorafenib was exhibited and which was paralleled by reducing Akt activation and inducing autophagy. These data suggest that our unique gene expression-screening platform allows efficient identification of underlying mechanisms of phytochemicals to overcome drug resistance of cancer cells.