a Department of Clinical Pharmacology, Xiangya Hospital , Central South University , Changsha , China.
b Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics , Central South University , Changsha , China.
Nutr Cancer. 2019;71(3):472-482. doi: 10.1080/01635581.2018.1516788. Epub 2018 Oct 29.
Although irinotecan is an important anticancer drug for treating colorectal cancer, its dose-dependent side effects limited its clinical application. Thus, it's important to develop low-toxic candidates to enhance the efficacy of irinotecan. Polyynes from genus Oplopanax were reported to possess potential anticancer effects on colorectal cancer. Hereby, we evaluated the synergetic inhibition of human colorectal cancer cells by combining polyyne-enriched fraction from Oplopanax elatus (the dichloromethane fraction of Oplopanax elatus, OED) and irinotecan. The results showed that 5 μg/ml of OED combined with 40 μM of irinotecan possessed significant synergetic inhibition on SW-480 cells with a combination index (CI) of 0.56. Besides, the percentage of apoptotic cells was significantly increased from 69.57% (40 μM of irinotecan) or 72.7% (5 μg/ml of OED) to 95.6% after treatment of OED combined with irinotecan (OCI), suggesting OED and irinotecan possess the synergistic apoptotic effect (P < 0.01). Furthermore, Caspase-3 was significantly activated in OCI group (P < 0.05). Besides, the percentage of apoptotic cells of OED or/and irinotecan significantly decreased after inhibition of caspase-3. These data indicated that OED could enhance antiproliferative effects of irinotecan on colorectal cancer cells, which was related with induction of apoptosis and regulations of activity of caspase-3.
尽管伊立替康是治疗结直肠癌的一种重要抗癌药物，但它的剂量依赖性副作用限制了其临床应用。因此，开发低毒的候选药物以增强伊立替康的疗效非常重要。五加科植物(Oplopanax)中的多炔类化合物被报道对结直肠癌具有潜在的抗癌作用。在此，我们评估了将来自 Oplopanax elatus 的富含多炔的馏分（Oplopanax elatus 的二氯甲烷馏分，OED）与伊立替康联合使用对人结直肠癌细胞的协同抑制作用。结果表明，5μg/ml 的 OED 与 40μM 的伊立替康联合使用对 SW-480 细胞具有显著的协同抑制作用，组合指数（CI）为 0.56。此外，与单独使用伊立替康（40μM）或 OED（5μg/ml）相比，用 OED 联合伊立替康处理后，凋亡细胞的比例从 69.57%（40μM 的伊立替康）或 72.7%（5μg/ml 的 OED）显著增加至 95.6%（OCI），表明 OED 和伊立替康具有协同凋亡作用（P<0.01）。此外，在 OCI 组中 Caspase-3 被显著激活（P<0.05）。此外，用 Caspase-3 抑制剂处理后，OED 或/和伊立替康诱导的凋亡细胞的比例显著降低。这些数据表明，OED 可以增强伊立替康对结直肠癌细胞的增殖抑制作用，这与诱导细胞凋亡和 Caspase-3 活性调节有关。
