Ge Lan, Wu Yaguang, Wan Ming, You Yi, Zhai Zhifang, Song Zhiqiang
Department of Dermatology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
Shumei Cosmetic Clinic in Lianhu District, Xi'an 710075, China.
J Oncol. 2021 Nov 29;2021:5525231. doi: 10.1155/2021/5525231. eCollection 2021.
Melanoma, also known as malignant melanoma, is a type of cancer derived from the pigment-containing cells known as melanocytes. Cisplatin (CDDP) is widely used in the treatment of different types of tumors with high response rates, but it generally has low efficiency in melanoma. This study aimed to investigate whether metformin could sensitize the melanoma cell line A375 to cisplatin. Our results for the first time indicated that CDDP increased the miR-34a secretion by exosomes in melanoma A375 cells, which was, at least partially, related to the cisplatin resistance of melanoma cells. Moreover, metformin significantly sensitized A375 cells to cisplatin. Mechanistically, metformin significantly blocked the exosome-mediated miR-34a secretion induced by cisplatin. Our study not only reveals a novel mechanism that exosomal secretion of miR-34a is involved in the cisplatin resistance of melanoma cells but also provides a promising therapeutic strategy by synergistic addition of metformin.
黑色素瘤，也称为恶性黑色素瘤，是一种源自称为黑素细胞的含色素细胞的癌症类型。顺铂（CDDP）广泛用于治疗不同类型的肿瘤，有效率较高，但它在黑色素瘤中的疗效通常较低。本研究旨在探讨二甲双胍是否能使黑色素瘤细胞系A375对顺铂敏感。我们的结果首次表明，CDDP增加了黑色素瘤A375细胞中外泌体分泌的miR-34a，这至少部分与黑色素瘤细胞的顺铂耐药性有关。此外，二甲双胍显著使A375细胞对顺铂敏感。从机制上讲，二甲双胍显著阻断了顺铂诱导的外泌体介导的miR-34a分泌。我们的研究不仅揭示了miR-34a的外泌体分泌参与黑色素瘤细胞顺铂耐药性的新机制，还通过联合添加二甲双胍提供了一种有前景的治疗策略。
