Mesbah Gholamreza, Namazi Fatemeh, T Shamsabadi Fatemeh, Maleki Zahra, Nasirikenari Mehrab, Shahbazi Majid
Department of Pathobiology, School of Veterinary Medicine, Shiraz University, Shiraz, Iran.
Medical Cellular and Molecular Research Center, Golestan University of Medical Sciences and Health Services, Gorgan, Iran.
Front Vet Sci. 2022 Aug 22;9:914311. doi: 10.3389/fvets.2022.914311. eCollection 2022.
Dysregulation of G1 cyclins (cyclins D1 A and E) expression contributes to the loss of standard cell cycle control during tumorigenesis. This study aims to evaluate the inhibitory effect of G1 cyclins in nude mice. The human breast cancer MDA-MB-231 cells were subcutaneously transplanted into the supra-femoral right side of female Balb/c-nude mice. The dual shRNA vector harboring G1 cyclins shRNAs (bipSUR) was intratumorally injected by the jetPEI transfection reagent for 2 weeks. We have evaluated tumor growth and tumor weight as parameters of tumor progression. Finally, necropsy, histopathological analysis, and immunodetection of G1 cyclins were assessed. Also, apoptosis induction in tumor tissues was evaluated by TUNEL assay. No toxicity and metastasis was observed in the tumor-bearing mice treated by the bipSUR. Tumor weight and volume were significantly lower in the bipSUR treated mice than untreated tumor-bearing mice and control. Histopathological observations revealed more apoptotic foci and lower mitotic cells in tumor sections in the treated mice than in control groups. A significant reduction of G1 cyclins at the protein level was indicated in the bipSUR treated mice than in other groups. Apoptosis in tumor tissues was remarkably induced in response to the bipSUR (42.53%). The bipSUR reduced the protein expression of G1 cyclins and exhibited an inhibitory effect on MDA-MB-231 xenograft mice through apoptosis induction. Further research is demanded to identify the protein partners of G1 cyclins involved in the cancer pathways. These may offer new insight into the biomedical function of G1 cyclins in breast cancer progression.
G1 细胞周期蛋白（细胞周期蛋白 D1、A 和 E）表达失调导致肿瘤发生过程中标准细胞周期控制的丧失。本研究旨在评估 G1 细胞周期蛋白对裸鼠的抑制作用。将人乳腺癌 MDA-MB-231 细胞皮下移植到雌性 Balb/c 裸鼠的右侧股上部。通过 jetPEI 转染试剂将携带 G1 细胞周期蛋白 shRNAs 的双 shRNA 载体（bipSUR）瘤内注射 2 周。我们评估了肿瘤生长和肿瘤重量作为肿瘤进展的参数。最后，进行尸检、组织病理学分析以及 G1 细胞周期蛋白的免疫检测。此外，通过 TUNEL 法评估肿瘤组织中的细胞凋亡诱导情况。接受 bipSUR 治疗的荷瘤小鼠未观察到毒性和转移。与未治疗的荷瘤小鼠和对照组相比，接受 bipSUR 治疗的小鼠的肿瘤重量和体积显著更低。组织病理学观察显示，治疗组小鼠肿瘤切片中的凋亡灶比对照组更多，有丝分裂细胞更少。与其他组相比，接受 bipSUR 治疗的小鼠中 G1 细胞周期蛋白的蛋白质水平显著降低。bipSUR 显著诱导了肿瘤组织中的细胞凋亡（42.53%）。bipSUR 通过诱导细胞凋亡降低了 G1 细胞周期蛋白的蛋白质表达，并对 MDA-MB-231 异种移植小鼠表现出抑制作用。需要进一步研究以确定参与癌症通路的 G1 细胞周期蛋白的蛋白质伙伴。这些可能为 G1 细胞周期蛋白在乳腺癌进展中的生物医学功能提供新的见解。
