HA15 inhibits binding immunoglobulin protein and enhances the efficacy of radiation therapy in esophageal squamous cell carcinoma

被引：3

作者：

Luo, Hui ^{[1
]}

Wang, Liuxiang ^{[2
]}

Zhang, Deju ^{[3
]}

Sun, Yanan ^{[1
]}

Wang, Shujuan ^{[1
]}

Song, Shuai ^{[1
]}

Ge, Hong ^{[1
,4
]}

机构：

[1] Zhengzhou Univ, Affiliated Canc Hosp, Dept Radiat Oncol, Zhengzhou, Peoples R China

[2] Zhengzhou Univ, Acad Med Sci, Zhengzhou, Peoples R China

[3] Univ Hong Kong, Sch Biol Sci, Food & Nutr Sci, Hong Kong, Peoples R China

[4] Zhengzhou Univ, Affiliated Canc Hosp, Dept Radiat Oncol, 127 Dongming Rd, Zhengzhou 450008, Henan, Peoples R China

来源：

CANCER SCIENCE | 2023年 / 114卷 / 04期

基金：

中国国家自然科学基金;

关键词：

binding immunoglobulin protein; endoplasmic reticulum stress; esophageal squamous cell carcinoma; immunogenic cell death; radiation therapy; ENDOPLASMIC-RETICULUM STRESS; LUNG-CANCER; DEATH; SENSITIVITY; COMPLEMENT; AUTOPHAGY;

D O I：

10.1111/cas.15712

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Proteomic profiling is a promising approach to identify novel predictors of radiation response. The present study aimed to identify potential biomarkers of radiation response by serum proteomics in esophageal squamous cell carcinoma (ESCC) patients and find efficacious therapeutic drugs to enhance the efficacy of radiation therapy (RT). Serum binding immunoglobulin protein (BIP) was identified and validated as a treatment response predictor in ESCC patients treated with RT. Novel BIP inhibitor HA15 showed antitumor activity in ESCC cells by viability assay. Tumor cell colony formation and apoptosis assay revealed targeting BIP was associated with significant improvements of radiation sensitivity. Further analyses revealed that HA15 enhanced radiation-induced endoplasmic reticulum (ER) stress and immunogenic cell death (ICD) in ESCC. Clinical data indicated that high expression of BIP was associated with poor survival in patients of ESCC. In conclusion, proteomics analysis suggested BIP was a promising predictor of radiation response in locally advanced ESCC. The BIP inhibitor HA15 acted as an ER stress inducer and ICD stimulator; RT combined with HA15 was effective in suppressing the growth of ESCC in vitro and in vivo. Pretreatment BIP was an essential prognostic biomarker in locally advanced ESCC patients treated with RT.

引用

页码：1697 / 1709

页数：13