西亚试剂：Essential Role of TRPC6 Channels in G2/M Phase Transition a

发布时间：2025-06-17

Essential Role of TRPC6 Channels in G2/M Phase Transition and Development of Human Glioma
Xia Ding, Zhuohao He, Kechun Zhou, Ju Cheng, Hailan Yao, Dongliang Lu, Rong Cai, Yening Jin, Bin Dong, Yinghui Xu, Yizheng Wang

Affiliations of authors: Laboratory of Neural Signal Transduction, Institute of Neuroscience, Shanghai Institute for Biological Sciences, State Key Laboratory of Neuroscience (XD, ZH, KZ, JC, HY, DL, YW) and Graduate School (XD, ZH, KZ, JC, HY, DL), Chinese Academy of Sciences, Shanghai, China; Ruijin Hospital, Department of Radiochemotherapy, Jiaotong University School of Medicine, Shanghai, China (RC, YJ); Department of Neurosurgery, First Affiliated Hospital of Dalian Medical University, Dalian, China (BD, YX)

Background: Patients with glioblastoma multiforme, the most aggressive form of glioma, have a median survival of approximately 12 months. Calcium (Ca2+) signaling plays an important role in cell proliferation, and some members of the Ca2+-permeable transient receptor potential canonical (TRPC) family of channel proteins have demonstrated a role in the proliferation of many types of cancer cells. In this study, we investigated the role of TRPC6 in cell cycle progression and in the development of human glioma.

Methods: TRPC6 protein and mRNA expression were assessed in glioma (n = 33) and normal (n = 17) brain tissues from patients and in human glioma cell lines U251, U87, and T98G. Activation of TRPC6 channels was tested by platelet-derived growth factor–induced Ca2+ imaging. The effect of inhibiting TRPC6 activity or expression using the dominant-negative mutant TRPC6 (DNC6) or RNA interference, respectively, was tested on cell growth, cell cycle progression, radiosensitization of glioma cells, and development of xenografted human gliomas in a mouse model. The green fluorescent protein (GFP) and wild-type TRPC6 (WTC6) were used as controls. Survival of mice bearing xenografted tumors in the GFP, DNC6, and WTC6 groups (n = 13, 15, and 13, respectively) was compared using Kaplan–Meier analysis. All statistical tests were two-sided.

Results: Functional TRPC6 was overexpressed in human glioma cells. Inhibition of TRPC6 activity or expression attenuated the increase in intracellular Ca2+ by platelet-derived growth factor, suppressed cell growth and clonogenic ability, induced cell cycle arrest at the G2/M phase, and enhanced the antiproliferative effect of ionizing radiation. Cyclin-dependent kinase 1 activation and cell division cycle 25 homolog C expression regulated the cell cycle arrest. Inhibition of TRPC6 activity also reduced tumor volume in a subcutaneous mouse model of xenografted human tumors (P = .014 vs GFP; P < .001 vs WTC6) and increased mean survival in mice in an intracranial model (P < .001 vs GFP or WTC6).

Conclusions: In this preclinical model, TRPC6 channels were essential for glioma development via regulation of G2/M phase transition. This study suggests that TRPC6 might be a new target for therapeutic intervention of human glioma.

• 以上资料由西亚试剂：http://www.xiyashiji.com/ 提供此产品的详细信息如密度,含量,分子式,分子量等均可在西亚官网查询   
• 相关产品如汞乙酸汞氯化汞氧化汞碘化汞硫酸汞硝酸汞溴化汞硝酸亚汞氯化亚汞乙酸苯汞碘化汞钾硫氰酸汞氯化氨基汞三氯生三氯氧磷三氯乙烯水合氯醛三氯化磷三氯化钌三氯化钛三氯化铱三氯化铑三氯硫磷三氯乙烷三氯甲烷三氯卡班TCC1,3,5-三氯苯1,2,4-三氯苯1,2,3-三氯苯无水氯化铝三氯乙酸酐三氯乙酸钠碘甲烷二碘甲烷三碘甲烷 三氟碘甲烷硫酸二甲酯氯磺酸苯硫酚苯硫酚钠3-氨基苯硫酚2,6-二氯苯硫酚2,4-二氯苯硫酚2,5-二氯苯硫酚2-甲氧基苯硫酚2-氯乙醇 等均有销售.欢迎订购

上一篇：西亚试剂 ：Cell：绘制广泛天然免疫网络图谱
下一篇：西亚试剂：两种蛋白在细胞内可形成自噬体细胞器