Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing 210009, China.
Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, China.
Biomed Pharmacother. 2017 May;89:1277-1285. doi: 10.1016/j.biopha.2017.02.104. Epub 2017 Mar 17.
Vinorelbine (NVB) is a semi-synthetic vinca alkaloid that is approved for the clinical therapy of lung cancer. However, the clinical application of NVB was limited because of the acquisition of resistance and inacceptable toxicity. Therefore, it is of great interest to develop low-cytotoxic drugs that can synergize with NVB. DT-13, a saponin monomer 13 of the Dwarf lilyturf tuber, showed inhibitory effects on tumor metastasis and angiogenesis in the previous studies. Here, we found that DT-13 combined with NVB exhibited synergistic effect to inhibit the cell proliferation in human lung cancer NCI-H1299 cells rather than human embryonic lung fibroblasts WI-38. The combination of DT-13 and NVB significantly inhibited the colony formation, induced cellular and nuclear morphological changes, and triggered cell cycle arrest at mitotic phase. Furthermore, MAPK signaling pathway was activated by the combination treatment, and the activation of ERK was required for the induction of mitotic arrest. Taken together, DT-13 combined with NVB exhibited synergistic anticancer effect in NCI-H1299 cells, and DT-13 may be a candidate agent for adjuvant chemotherapy of NVB in lung cancer.
长春瑞滨（NVB）是一种半合成长春碱类药物，已被批准用于肺癌的临床治疗。然而，由于获得耐药性和不可接受的毒性，NVB 的临床应用受到限制。因此，开发与 NVB 协同作用的低细胞毒性药物具有重要意义。在之前的研究中，麦冬皂苷单体 13（DT-13）表现出抑制肿瘤转移和血管生成的作用。在这里，我们发现 DT-13 与 NVB 联合使用可协同抑制人肺癌 NCI-H1299 细胞而不是人胚肺成纤维细胞 WI-38 的增殖。DT-13 和 NVB 的联合使用显著抑制集落形成，诱导细胞和核形态变化，并触发有丝分裂期细胞周期停滞。此外，MAPK 信号通路被联合治疗激活，ERK 的激活对于诱导有丝分裂停滞是必需的。综上所述，DT-13 与 NVB 联合在 NCI-H1299 细胞中表现出协同抗癌作用，DT-13 可能是 NVB 肺癌辅助化疗的候选药物。
