磷脂酰肌醇3激酶CB与直肠腺癌术前放疗反应的关联

Phosphatidylinositol 3-kinase CB association with preoperative radiotherapy response in rectal adenocarcinoma.

作者信息

Yu Wei-Dong, Peng Yi-Fan, Pan Hong-Da, Wang Lin, Li Kun, Gu Jin

机构信息

Wei-Dong Yu, Kun Li, Institute of Clinical Molecular Biology, People's Hospital, Peking University, Beijing 100044, China.

出版信息

World J Gastroenterol. 2014 Nov 21;20(43):16258-67. doi: 10.3748/wjg.v20.i43.16258.

DOI:10.3748/wjg.v20.i43.16258

PMID:25473181

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4239515/

Abstract

AIM

To examine the correlation of phosphatidylinositol 3-kinase (PIK3) CB expression with preoperative radiotherapy response in patients with stage II/III rectal adenocarcinoma.

METHODS

PIK3CB immunoexpression was retrospectively assessed in pretreatment biopsies from 208 patients with clinical stage II/III rectal adenocarcinoma, who underwent radical surgery after 30-Gy/10-fraction preoperative radiotherapy. The relation between PIK3CB expression and tumor regression grade, clinicopathological characteristics, and survival time was statistically analyzed. Western blotting and in vitro clonogenic formation assay were used to detect PIK3CB expression in four colorectal cancer cell lines (HCT116, HT29, LoVo, and LS174T) treated with 6-Gy ionizing radiation. Pharmacological assays were used to evaluate the therapeutic relevance of TGX-221 (a PIK3CB-specific inhibitor) in the four colorectal cancer cell lines.

RESULTS

Immunohistochemical staining indicated that PIK3CB was more abundant in rectal adenocarcinoma tissues with poor response to preoperative radiotherapy. High expression of PIK3CB was closely correlated with tumor height (P < 0.05), ypT stage (P < 0.05), and high-degree tumor regression grade (P < 0.001). High expression of PIK3CB was a potential prognostic factor for local recurrence-free survival (P < 0.05) and metastasis-free survival (P < 0.05). High expression of PIK3CB was also associated with poor therapeutic response and adverse outcomes in rectal adenocarcinoma patients treated with 30-Gy/10-fraction preoperative radiotherapy. In vitro, PIK3CB expression was upregulated in all four colorectal cancer cell lines concurrently treated with 6-Gy ionizing radiation, and the PIK3CB-specific inhibitor TGX-221 effectively inhibited the clonogenic formation of these four colorectal cancer cell lines.

CONCLUSION

PIK3CB is critically involved in response to preoperative radiotherapy and may serve as a novel target for therapeutic intervention.

摘要

目的

探讨磷脂酰肌醇3激酶（PIK3）CB表达与II/III期直肠腺癌患者术前放疗反应的相关性。

方法

回顾性评估208例临床II/III期直肠腺癌患者治疗前活检组织中的PIK3CB免疫表达情况，这些患者接受了30 Gy/10次分割的术前放疗后行根治性手术。对PIK3CB表达与肿瘤退缩分级、临床病理特征及生存时间的关系进行统计学分析。采用蛋白质免疫印迹法和体外克隆形成试验检测6 Gy电离辐射处理的四种结肠癌细胞系（HCT116、HT29、LoVo和LS174T）中PIK3CB的表达。采用药理学试验评估TGX-221（一种PIK3CB特异性抑制剂）对这四种结肠癌细胞系的治疗相关性。

结果

免疫组织化学染色显示，对术前放疗反应较差的直肠腺癌组织中PIK3CB表达更为丰富。PIK3CB高表达与肿瘤高度（P<0.05）、ypT分期（P<0.05）及高度肿瘤退缩分级（P<0.001）密切相关。PIK3CB高表达是局部无复发生存（P<0.05）和无转移生存（P<0.05）的潜在预后因素。PIK3CB高表达还与接受30 Gy/10次分割术前放疗的直肠腺癌患者的治疗反应差和不良结局相关。在体外，同时接受6 Gy电离辐射处理的所有四种结肠癌细胞系中PIK3CB表达均上调，且PIK3CB特异性抑制剂TGX-221有效抑制了这四种结肠癌细胞系的克隆形成。