Weng Jiefeng, Liu Hui, Wu Zhaofeng, Huang Yu, Zhang Shuai, Xu Yujie
Department of Hepatobiliary Pancreatic Surgery, Guangzhou First People's Hospital, Guangzhou City, China.
Physical Examination Center, Guangzhou First People's Hospital, Guangzhou City, China.
Biomol Biomed. 2025 Mar 7;25(4):857-868. doi: 10.17305/bb.2024.10928.
The aim of this research was to investigate the impact of periplocin (PPLN) on oxaliplatin (OXA) resistance in hepatocellular carcinoma (HCC) cells and offer insights for improving clinical treatment of HCC. The IC50 value of HCC cell lines against OXA was detected by the CCK-8 assay, and an OXA-resistant HepG2 cell line (HepG2/OXA) was constructed. THP-1 cells were induced into M1 or M2 macrophages, and M2 macrophage-conditioned medium (M2-CM) was prepared. M1 and M2 macrophage polarization were detected using RT-qPCR and flow cytometry. CCK-8, EdU staining, clone formation assay, flow cytometry, and western blotting were used to assess the proliferation and apoptosis of HepG2/OXA cells treated with PPLN and M2-CM. Additionally, a nude mouse subcutaneous graft tumor model was constructed. PPLN enhanced the sensitivity of HepG2/OXA cells to OXA, reduced their clone-forming ability, and promoted their apoptosis. Notably, PPLN hindered M0 macrophage polarization to M2 macrophages, while M1 polarization remained unaffected. The proliferation-inhibiting and apoptosis-promoting effects of OXA+PPLN on HepG2/OXA cells were significantly attenuated by the addition of M2-CM, suggesting that PPLN improves the OXA sensitivity of HepG2/OXA cells by hindering M2 macrophage polarization. Furthermore, PPLN inhibited M2 macrophage polarization and improved the OXA sensitivity of HepG2/OXA cells in vivo. In conclusion, PPLN inhibited the proliferation of HepG2/OXA cells, promoted their apoptosis, and inhibited M2 macrophage polarization both in vivo and in vitro, which in turn enhanced the OXA sensitivity of HepG2/OXA cells.
本研究旨在探讨杠柳毒苷（PPLN）对肝癌（HCC）细胞中奥沙利铂（OXA）耐药性的影响，并为改善HCC的临床治疗提供见解。通过CCK-8法检测HCC细胞系对OXA的IC50值，并构建奥沙利铂耐药的HepG2细胞系（HepG2/OXA）。将THP-1细胞诱导为M1或M2巨噬细胞，并制备M2巨噬细胞条件培养基（M2-CM）。采用RT-qPCR和流式细胞术检测M1和M2巨噬细胞极化。使用CCK-8、EdU染色、克隆形成试验、流式细胞术和蛋白质免疫印迹法评估用PPLN和M2-CM处理的HepG2/OXA细胞的增殖和凋亡。此外，构建了裸鼠皮下移植瘤模型。PPLN增强了HepG2/OXA细胞对OXA的敏感性，降低了其克隆形成能力，并促进了其凋亡。值得注意的是，PPLN阻碍了M0巨噬细胞向M2巨噬细胞的极化，而M1极化不受影响。添加M2-CM后，OXA+PPLN对HepG2/OXA细胞的增殖抑制和促凋亡作用显著减弱，表明PPLN通过阻碍M2巨噬细胞极化提高了HepG2/OXA细胞对OXA的敏感性。此外，PPLN在体内抑制了M2巨噬细胞极化并提高了HepG2/OXA细胞对OXA的敏感性。总之，PPLN在体内和体外均抑制了HepG2/OXA细胞的增殖，促进了其凋亡，并抑制了M2巨噬细胞极化，进而增强了HepG2/OXA细胞对OXA的敏感性。
