Microbiology and Immunology Department, Guangdong Medical University, Dongguan, 523808, China.
Pathology Department of The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, 523713, China.
J Cancer Res Clin Oncol. 2024 Aug 3;150(8):380. doi: 10.1007/s00432-024-05904-1.
This study aims to determine whether Pokemon regulates Bim activity in colorectal carcinoma (CRC) carcinogenesis.
Clinical tissue samples were analyzed to detect the expression and clinicopathological significance of Pokemon and Bim in CRC. Proliferation, apoptosis, and invasion assays were conducted to identify the regulatory effect of Pokemon on Bim. The combined treatment effects of Pokemon knockdown and diamminedichloroplatinum (DDP) were also examined.
Immunohistochemical analysis of 80 samples of colorectal epithelia (CRE), 80 cases of colorectal adenoma (CRA), and 160 of CRC samples revealed protein expression rates of 23.8%, 38.8%, and 70.6% for Pokemon, and 88.8%, 73.8%, and 31.9% for Bim, respectively. A significant negative correlation was observed between Pokemon and Bim expression across the CRE, CRA, and CRC lesion stages. In CRC, higher Pokemon and lower Bim expression correlated with higher histological grades, advanced Dukes stages, and increased cancer invasion. In both LoVo and HCT116 cells, overexpression of Pokemon significantly reduced Bim expression, leading to increased proliferation, resistance to anoikis, and cell invasion. Additionally, Pokemon overexpression significantly decreased DDP-induced Bim expression, reduction of anti-apoptosis and invasion, whereas Pokemon knockdown resulted in the opposite effects.
These findings suggest that Pokemon inhibits Bim transcription, thereby promoting CRC proliferation, resistance to apoptosis, invasion, and advancing histological grade and Dukes staging. Pokemon knockdown enhances the therapeutic efficacy of DDP in the treatment of CRC.
本研究旨在确定口袋妖怪是否调节结直肠癌（CRC）癌变过程中的 Bim 活性。
分析临床组织样本，以检测 CRC 中口袋妖怪和 Bim 的表达及其临床病理意义。进行增殖、凋亡和侵袭测定，以鉴定口袋妖怪对 Bim 的调节作用。还检查了口袋妖怪敲低和二氨二氯铂（DDP）联合治疗的效果。
对 80 例结直肠上皮（CRE）、80 例结直肠腺瘤（CRA）和 160 例 CRC 样本进行免疫组织化学分析，结果显示口袋妖怪的蛋白表达率分别为 23.8%、38.8%和 70.6%，Bim 的蛋白表达率分别为 88.8%、73.8%和 31.9%。在 CRE、CRA 和 CRC 病变阶段，口袋妖怪和 Bim 的表达呈显著负相关。在 CRC 中，较高的口袋妖怪和较低的 Bim 表达与较高的组织学分级、较晚的 Dukes 分期和增加的癌症侵袭相关。在 LoVo 和 HCT116 细胞中，口袋妖怪的过表达显著降低了 Bim 的表达，导致增殖增加、抗凋亡和细胞侵袭增强。此外，口袋妖怪的过表达还显著降低了 DDP 诱导的 Bim 表达，减少了抗凋亡和侵袭，而口袋妖怪的敲低则产生了相反的效果。
这些发现表明口袋妖怪抑制 Bim 转录，从而促进 CRC 的增殖、抗凋亡、侵袭以及组织学分级和 Dukes 分期的进展。口袋妖怪敲低增强了 DDP 在 CRC 治疗中的疗效。
