Department of Biochemistry and Microbiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, 10330, Thailand.
Department of Pharmacy, School of Health Care Professions, University of San Carlos, 6000, Cebu, Philippines.
Sci Rep. 2021 Feb 18;11(1):4060. doi: 10.1038/s41598-021-83606-1.
The limitations of cisplatin, a standard chemotherapy for lung cancer, have been documented with serious adverse effects and drug resistance. To address the need for novel therapy, this study firstly reveals the potential of peptide from Lentinus squarrosulus (Mont.) as a chemotherapeutic adjuvant for cisplatin treatment. The purified peptide from L. squarrosulus aqueous extracts was obtained after eluting with 0.4 M NaCl through FPLC equipped with anion exchange column. Preincubation for 24 h with 5 µg/mL of the peptide at prior to treatment with 5 µM cisplatin significantly diminished %cell viability in various human lung cancer cells but not in human dermal papilla and proximal renal cells. Flow cytometry indicated the augmentation of cisplatin-induced apoptosis in lung cancer cells pretreated with peptide from L. squarrosulus. Preculture with the peptide dramatically inhibited colony formation in lung cancer cells derived after cisplatin treatment. Strong suppression on integrin-mediated survival was evidenced with the diminution of integrins (β1, β3, β5, α5, αV) and down-stream signals (p-FAK/FAK, p-Src/Src, p-Akt/Akt) consequence with alteration of p53, Bax, Blc-2 and Mcl-1 in cisplatin-treated lung cancer cells preincubated with peptide from L. squarrosulus. These results support the development of L. squarrosulus peptide as a novel combined chemotherapy with cisplatin for lung cancer treatment.
顺铂作为肺癌的标准化疗药物，其局限性已被证实存在严重的不良反应和耐药性。为了解决新疗法的需求，本研究首先揭示了香菇肽作为顺铂治疗的化疗辅助剂的潜力。从香菇水提物中通过 FPLC 配备阴离子交换柱，用 0.4 M NaCl 洗脱，获得纯化的肽。用 5 µM 顺铂处理前，用 5 µg/mL 的肽预孵育 24 h，可显著降低各种人肺癌细胞的 %细胞活力，但对人真皮乳头和近端肾细胞没有影响。流式细胞术表明，香菇肽预处理可增强顺铂诱导的肺癌细胞凋亡。肽预培养可显著抑制顺铂处理后肺癌细胞的集落形成。用香菇肽处理后，整合素介导的存活受到强烈抑制，整合素（β1、β3、β5、α5、αV）和下游信号（p-FAK/FAK、p-Src/Src、p-Akt/Akt）减少，导致 p53、Bax、Bcl-2 和 Mcl-1 改变，这证实了这一点顺铂处理的肺癌细胞。这些结果支持开发香菇肽作为一种新型联合化疗药物，与顺铂联合用于肺癌治疗。
