College of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, China.
ReMed Biotechnology Co.Ltd, Hefei, 230031, China.
Biochem Biophys Res Commun. 2019 Jan 15;508(3):882-888. doi: 10.1016/j.bbrc.2018.12.028. Epub 2018 Dec 8.
Gambogenic acid (GNA), an active ingredient isolated from Gamboge, which possesses diverse antitumor effects in vivo and vitro. Here we were mainly designed to understand the role of GNA in drug resistance in HepG2/Adr cells. The alteration of cytotoxic drugs IC was examined using the MTT method. Cell apoptosis and uptake of P-glycoprotein (P-gp) substrates were measured under a flow cytometry and fluorescence microscope, respectively. Moreover, the ATPase activity, the expression of P-gp and P-gp-related proteins were also investigated. Results of the MTT method indicated that GNA increased the chemosensitivity of doxorubicin (DOX) and paclitaxel (PTX) in the HepG2/Adr cells and promoted the cell apoptosis in the presence of DOX. Meanwhile, it was also increased the retention of P-gp substrates DOX and Rhodamine 123 (Rho-123) while did not affect the ATPase activity. Furthermore, the down-regulation of P-gp expression could be contributed to multidrug resistance (MDR) upon a reversal concentration of 0.8 μg/mL GNA. Mechanistically, the expression of P-gp was reduced by GNA may result from the inhibition of the NF-kB and MAPK pathway. Collectively, GNA could be a potential inhibitor to reverse P-gp-mediated MDR in liver cancer therapy.
吉马酮酸（GNA）是从藤黄中分离得到的一种活性成分，具有体内和体外多种抗肿瘤作用。本研究主要旨在探讨 GNA 在 HepG2/Adr 细胞耐药中的作用。采用 MTT 法检测细胞毒性药物 IC 的变化。采用流式细胞术和荧光显微镜分别测定细胞凋亡和 P-糖蛋白（P-gp）底物摄取。此外，还研究了 ATP 酶活性、P-gp 及其相关蛋白的表达。MTT 法结果表明，GNA 增加了多柔比星（DOX）和紫杉醇（PTX）在 HepG2/Adr 细胞中的化疗敏感性，并在 DOX 存在下促进细胞凋亡。同时，它还增加了 P-gp 底物 DOX 和罗丹明 123（Rho-123）的保留率，而不影响 ATP 酶活性。此外，在 0.8μg/mL GNA 的逆转浓度下，P-gp 表达的下调可能导致多药耐药（MDR）。在机制上，GNA 可能通过抑制 NF-κB 和 MAPK 通路来降低 P-gp 的表达。综上所述，GNA 可能是一种有潜力的抑制剂，可逆转肝癌治疗中的 P-gp 介导的多药耐药。
