Department of Immunology, College of Basic Medical Science, China Medical University, Shenyang, Liaoning 110122, P.R. China.
Center for Translational Medicine, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning 110032, P.R. China.
Oncol Rep. 2017 Oct;38(4):2132-2140. doi: 10.3892/or.2017.5918. Epub 2017 Aug 24.
Melanoma is a common cutaneous malignancy, that is also found in specific mucosal sites, and is associated with a poor prognosis. The aim of the present study was to investigate the cytotoxicity of methionine enkephalin (MENK) for B16 melanoma cells in vivo and in vitro. The results of the present study allowed our conclusion that MENK regulates the proliferation of B16 cells, causing cell cycle arrest in the G0/G1 phase and a decrease in the percentage of cells in the S and G2/M phases. Reverse transcription-quantitative polymerase chain reaction demonstrated that MENK increased opioid receptor expression in the B16 cells. Furthermore, the tumor volume and weight in the MENK-treated group were lower than those in the control group (NS) and MENK and naltrexone (NTX)-treated groups. MENK exerted both significant antitumor activity on the growth of B16 cells and a longer survival time in mice. The mice treated with MENK exhibited an increased ratio of CD4+ to CD8+ T cells as tested by flow cytometry (FCM), resulting in a ratio of 2.03 in the control group, 3.69 in the MENK-treated group, and 2.65 in the MENK and NTX group. Furthermore, a significant increase in plasma levels of IL-2, IFN-γ and TNF-α was revealed as assessed by ELISA. In conclusion, the results of the present study indicate that MENK has a cytotoxic effect on B16 melanoma cells in vitro and in vivo, and suggest a potential mechanism for these bioactivities. Therefore, we posit that MENK should be investigated, not only as a primary therapy for melanoma, but also as an adjuvant therapy in combination with chemotherapies.
黑色素瘤是一种常见的皮肤恶性肿瘤，也存在于特定的黏膜部位，并与预后不良相关。本研究旨在探讨甲硫氨酸脑啡肽（MENK）对 B16 黑色素瘤细胞的体内和体外细胞毒性。本研究的结果表明，MENK 调节 B16 细胞的增殖，导致细胞周期停滞在 G0/G1 期，S 期和 G2/M 期细胞百分比下降。逆转录定量聚合酶链反应表明，MENK 增加了 B16 细胞中阿片受体的表达。此外，MENK 治疗组的肿瘤体积和重量低于对照组（NS）和 MENK 和纳曲酮（NTX）治疗组。MENK 对 B16 细胞的生长既具有显著的抗肿瘤活性，又能延长小鼠的生存时间。通过流式细胞术（FCM）检测，MENK 治疗组的 CD4+/CD8+T 细胞比值增加，对照组为 2.03，MENK 治疗组为 3.69，MENK 和 NTX 治疗组为 2.65。此外，ELISA 检测显示，血浆中 IL-2、IFN-γ 和 TNF-α 的水平显著升高。综上所述，本研究结果表明，MENK 对体外和体内的 B16 黑色素瘤细胞具有细胞毒性作用，并提示了这些生物活性的潜在机制。因此，我们认为不仅应将 MENK 作为黑色素瘤的主要治疗方法进行研究，还应将其作为化疗的辅助治疗方法进行研究。
