125I seeds inhibit proliferation and promote apoptosis in cholangiocarcinoma cells by regulating the AGR2-mediated p38 MAPK pathway

Zhou, Xueliang; Zhang, Wenguang; Dou, Mengmeng; Li, Zhaonan; Liu, Zaoqu; Li, Jing; Tian, Chuan; Yao, Yuan; Wang, Chaoyan; Li, Yahua; Chen, Pengfei; Han, Xinwei; Jiao, Dechao

doi:10.1016/j.canlet.2021.10.014

Cited by 16 publications

(12 citation statements)

References 38 publications

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“…Similarly, previous studies also demonstrated that the cancer killing effect of I-125 seed radiation was dependent on inducing cell cycle arrest and apoptosis in gastric cancer [9], lung cancer [21] and pancreatic cancer cells [22]. In addition, a recent in vitro and in vivo study showed that I-125 seeds inhibited the proliferation and promoted apoptosis of CCA cells by increasing the expression of p-p38 MAPK and p-p53 [23]. These data at least partly supported our results that the molecular mechanism of I-125 seed irradiation involved inhibition of CCA cell viability, cell cycle progression and promotion of cell apoptosis.…”

Section: Discussionmentioning

confidence: 65%

Iodine-125 induced cholangiocarcinoma cell death is enhanced by inhibition of endoplasmic reticulum stress-mediated protective autophagy

Zou

Chang

Bai

et al. 2022

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Cholangiocarcinoma (CCA) is the second most common primary liver malignancy, however, it is difficult to diagnose and treat, and only a few patients with CCA are suitable for surgery. Iodine-125 (I-125) is an effective treatment for cancer, but the molecular mechanisms underlying the effects of I-125 differ among different cancers. This study aimed to explore the effects of I-125 on CCA cell activity and determine the possible mechanisms of action of I-125 in this type of cancer. CCA cell proliferation, cycling, apoptosis, autophagy, and endoplasmic reticulum (ER) stress were determined after irradiation of CCA cells with I-125 seeds. The effects of I-125 on autophagy and ER stress in three CCA cell lines were evaluated using western blotting, while the effects of I-125 on apoptosis and autophagy in QBC939 cells treated with si-Beclin1 or si-PERK, respectively, were assessed using flow cytometry. I-125 suppressed cell viability and induced cell cycle G2/M-phase arrest in three CCA cell lines (QBC939, TFK-1, HuCCT1). I-125 induced apoptosis, autophagy, and ER stress by altering the expression levels of some related proteins in each of the three CCA cell lines. Furthermore, autophagy inhibition (treatment with si-Beclin1) increased expression of apoptosis-related proteins (Cleaved-PARP and Cleaved-caspase-3, Bax/Bcl2) in QBC939 cells irradiated with I-125 seeds, while ER stress inhibition (si-PERK) suppressed the expression of autophagy-related proteins (LC3-I, LC3-II, P62). Therefore, I-125 induces ER stress, thereby activating protective autophagy in CCA cells through the PERK signaling pathway. Combined inhibition of ER stress and autophagy signaling may increase the killing effect of I-125 on cancer cells and serve as a new auxiliary method in I-125 radiotherapy.

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Section: Discussionmentioning

confidence: 65%

Iodine-125 induced cholangiocarcinoma cell death is enhanced by inhibition of endoplasmic reticulum stress-mediated protective autophagy

Zou

Chang

Bai

et al. 2022

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“…AGR2 may inhibit the phosphorylation of p53 at Ser15 and Ser392 sites by targeting the plasma membrane, thereby preventing cell apoptosis. At the same time, AGR2 up-regulates dual specific phosphatase 10 (DUSP10) ( 43 , 44 ), thereby inhibiting p38 mitogen activated protein kinase (p38 MAPK) and preventing the activation of p53. MAPK/ERK signaling pathway may also be involved in the role of AGR2 in tumor ( 45 ).…”

Section: Agr2 and Interaction Partnersmentioning

confidence: 99%

AGR2: a secreted protein worthy of attention in diagnosis and treatment of breast cancer

Zhang

Kong

et al. 2023

Front. Oncol.

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AGR2 is a secreted protein widely existing in breast. In precancerous lesions, primary tumors and metastatic tumors, the expression of AGR2 is increased, which has aroused our interest. This review introduces the gene and protein structure of AGR2. Its endoplasmic reticulum retention sequence, protein disulfide isomerase active site and multiple protein binding sequences endow AGR2 with diverse functions inside and outside breast cancer cells. This review also enumerates the role of AGR2 in the progress and prognosis of breast cancer, and emphasizes that AGR2 can be a promising biomarker and a target for immunotherapy of breast cancer, providing new ideas for early diagnosis and treatment of breast cancer.

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“…What’s more, RISB for prostate cancer and brachytherapy stent loaded with 125 I seeds for malignant esophageal obstruction is recommended by some guidelines from the European Endoscopic Society and the Chinese Society for Esophageal Cancer Radiotherapy [ 13 , 14 ]. Compared with SBRT, both can achieve high dose radiation to tumors and minimize radiation injury to the surrounding normal tissue, but RISB has its own advantages [ 15 , 16 ]: (1) RISB can be widely applied under conventional CT without expensive SBRT equipment additionally; (2) all patients can complete RISB with warm home-care without frequent hospital visits; (3) RISB is cheaper for patients to reduce economic burden; (4) continuous low dose radiation is in accordance with radiotherapy “4R theory” such as repair of radiation damage, redistribution within cell cycle, reoxygenation of tumors, and repopulation of cells in tissue; (5) the local control rate (LCR) of lung tumors after RISB can be as high as 80%–96% in recent Meta analysis [ 17 ], causing relatively slighter radiation-induced lung injury that can be repeated in the short term [ 7 ], which gradually attracted the attention of radiotherapists, interventionists, oncologists and nuclide specialists. So can RISB achieve comparable efficacy to SBRT in LO from CRC?…”

Section: Introductionmentioning

confidence: 99%

CT-guided radioactive 125I seeds brachytherapy for lung oligometastases from colorectal cancer: initial results

Song,

Zhou,

Hou

et al. 2024

BMC Cancer

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Objectives To evaluate the safety and effectiveness of computed tomography (CT)-guided radioactive 125I seeds brachytherapy (RISB) for lung oligometastases (LO) from colorectal cancer (CRC). Methods Data for 144 LOs from 70 CRC patients who underwent CT-guided RISB were retrospectively analyzed. The primary endpoints were progression-free survival (PFS) and overall survival (OS), and the secondary endpoints were technical success, local control rate (LCR), and complications. Kaplan–Meier method was used for survival analysis. Cox model was used to identify the independent predictors of poor prognosis. Results The RISB procedures were successfully performed in all patients, and the success rate was 100%. The median follow-up was 27.8 months. The median PFS was 10.0 months (95% CI: 8.9–11.1) and the 1- and 2-year PFS rates were 32.9% and 5.9%, respectively. On multivariate analysis, serum carcinoembryonic antigen (CEA) ≤ 15 ng/ml (P = 0.048), middle-high differentiated pathological classification (P = 0.015), primary TNM stages I-III (P = 0.001), LO number ≤ 2 (P < 0.001) and cumulative gross tumor volume (GTV) ≤ 40 cm3 (P < 0.001) showed superior PFS. The median OS was 30.8 months (95% CI: 27.1–34.4) and the 1-, 2-, and 3-year OS rates were 95.7%, 67.4%, and 42.5%, respectively. On multivariate analysis, serum CEA ≤ 15 ng/ml (P = 0.004), middle-high differentiated pathological classification (P < 0.001), primary TNM stages I-III (P < 0.001), LO number ≤ 2 (P < 0.001), cumulative GTV ≤ 40 cm3 (P < 0.001) and system treatments combined with chemotherapy and target therapy (P < 0.001) showed superior OS. The LCR for 3, 6, and 12 months was 97.9%, 91.0%, and 83.6%, respectively. There were 4 cases of pneumothorax at 5.7% that required drainage. Conclusions RISB for LO from CRC is safe and effective, and serum CEA, TNM stage, LO number, cumulative GTV, and system treatments should be emphasized for long OS.

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125I seeds inhibit proliferation and promote apoptosis in cholangiocarcinoma cells by regulating the AGR2-mediated p38 MAPK pathway

Cited by 16 publications

References 38 publications

Iodine-125 induced cholangiocarcinoma cell death is enhanced by inhibition of endoplasmic reticulum stress-mediated protective autophagy

Iodine-125 induced cholangiocarcinoma cell death is enhanced by inhibition of endoplasmic reticulum stress-mediated protective autophagy

AGR2: a secreted protein worthy of attention in diagnosis and treatment of breast cancer

CT-guided radioactive 125I seeds brachytherapy for lung oligometastases from colorectal cancer: initial results

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