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水疱性口炎病毒 M51R 和 Delta-M51 基质蛋白诱导结直肠癌细胞凋亡。

M51R and Delta-M51 matrix protein of the vesicular stomatitis virus induce apoptosis in colorectal cancer cells.

机构信息

Department of Microbiology, College of Medicine, Golestan University of Medical Science, 1 Shastcola Ave, 5 km Sari Rd, Gorgan, Iran.

Cell and Molecular Research center, Golestan University of Medical Science, 1 Shastcola Ave, 5 km Sari Rd, Gorgan, Iran.

出版信息

Mol Biol Rep. 2019 Jun;46(3):3371-3379. doi: 10.1007/s11033-019-04799-3. Epub 2019 Apr 20.

Abstract

Colorectal cancer (CRC) is the third most common cancer in both men and women. Oncolytic viral-based therapy methods seem to be promising for CRC treatment. Vesicular stomatitis virus (VSV) is considered as a potent candidate in viral therapy for several tumors. VSV particles with mutated matrix (M) protein are capable of initiating cell death cascades while not being harmful to the immune system. In the current study, the effects of the VSV M-protein was investigated on the apoptosis of the colorectal cancer SW480 cell. Wild-type, M51R, and ΔM51 mutants VSV M-protein genes were cloned into the PCDNA3.1 vector and transfected into the SW480 cells. The results of the MTT assay, Western blotting, and Caspase 3, 8, and 9 measurement, illustrated that both wild and M51R mutant M-proteins can destroy the SW480 colorectal cancer cells. DAPI/TUNEL double-staining reconfirmed the apoptotic effects of the M-protein expression. The ΔM51 mutant M-protein is effective likewise M51R, somehow it can be considered as a safer substitution.

摘要

结直肠癌(CRC)是男性和女性中第三常见的癌症。溶瘤病毒为基础的治疗方法似乎对 CRC 治疗有很大的前景。水疱性口炎病毒(VSV)被认为是几种肿瘤病毒治疗的有效候选者。具有突变基质(M)蛋白的 VSV 颗粒能够引发细胞死亡级联反应,而对免疫系统没有危害。在本研究中,研究了 VSV M 蛋白对结直肠癌细胞 SW480 凋亡的影响。野生型、M51R 和 ΔM51 突变体 VSV M 蛋白基因被克隆到 PCDNA3.1 载体中,并转染到 SW480 细胞中。MTT 测定、Western blot 和 Caspase 3、8 和 9 测量的结果表明,野生型和 M51R 突变体 M 蛋白都可以破坏 SW480 结直肠癌细胞。DAPI/TUNEL 双重染色再次证实了 M 蛋白表达的凋亡作用。ΔM51 突变体 M 蛋白与 M51R 同样有效,它可以被认为是一种更安全的替代品。

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