Nanjing University of Chinese Medicine, Nanjing, P.R. China.
Yuhuatai District Maternity and Child Care Clinic, Nanjing, P.R. China.
Integr Cancer Ther. 2022 Jan-Dec;21:15347354221078888. doi: 10.1177/15347354221078888.
Hepatocellular carcinoma (HCC) is a high mortality liver cancer. The existing treatments (transplantation, chemotherapy, and individualized treatment) with limitations. However, drug combination provides a viable option for hepatocellular carcinoma treatment. A Chinese patent medicine, ShuangDan Capsules (SDC), has been clinically prescribed to hepatocellular carcinoma patients as adjuvant therapy and has shown good antitumor activity. The purpose of this study was to investigate whether SDC could improve the anti-cancer effect and mitigate adverse reactions of sorafenib on HCC in vivo. Magnetic resonance imaging (MRI), immunohistochemistry, and western blot were executed to reveal the potential mechanisms of the combination of SDC and sorafenib on HCC. Tumors appeared hyperintense on T2 sequence images relative to the adjacent normal liver in MRI. Combination of SDC and sorafenib inhibited the progression of DEN (Diethylnitrosamine)-induced HCC. In the HepG2 xenografts model, sorafenib plus SDC exhibited greater suppression on tumor growth than individual treatment accompanied with decreased expression of VEGF, VEGFA, Ki67, CD31 and increased expression of caspase-3. Furthermore, PI3K/Akt/mTORC1 pathway was inhibited by co-administration. Sorafenib monotherapy elicited hepatotoxicity for specific expression in the up-regulated level of aspartate transaminase (AST) and AST/glutamic-pyruvic transaminase (ALT) ratio, but the co-administration could remedy this adverse effect. These dates indicated that the combination of SDC and sorafenib might offer a potential therapy for HCC.
肝细胞癌（HCC）是一种高死亡率的肝癌。现有的治疗方法（移植、化疗和个体化治疗）存在局限性。然而，药物联合为肝癌治疗提供了可行的选择。一种中药复方丹参胶囊（SDC）已被临床用于肝癌患者的辅助治疗，并显示出良好的抗肿瘤活性。本研究旨在探讨 SDC 是否能提高索拉非尼对 HCC 的抗癌作用，并减轻其不良反应。磁共振成像（MRI）、免疫组织化学和 Western blot 用于揭示 SDC 和索拉非尼联合治疗 HCC 的潜在机制。在 MRI 中，肿瘤在 T2 序列图像上相对于相邻正常肝脏呈高信号。SDC 和索拉非尼联合抑制 DEN（二乙基亚硝胺）诱导的 HCC 进展。在 HepG2 异种移植模型中，索拉非尼加 SDC 组的肿瘤生长抑制作用大于单独治疗组，同时 VEGF、VEGFA、Ki67、CD31 的表达降低，caspase-3 的表达增加。此外，PI3K/Akt/mTORC1 通路也被抑制。索拉非尼单药治疗引起肝毒性，AST（天门冬氨酸转氨酶）和 AST/ALT（谷氨酸丙酮酸转氨酶）比值升高，但联合用药可纠正这种不良反应。这些数据表明，SDC 和索拉非尼联合治疗可能为 HCC 提供一种潜在的治疗方法。
