Yuting Wang1, Wen Zhang1, Lin Chen2, Wei Chen2, Shufen Xu3, Lingyu Tang1, Yang Yang1, Quanpeng Li4,5, Qi Jiang6, Lin Miao7. 1. Department of Medical Center for Digestive Diseases, The Second Affiliated Hospital, Nanjing Medical University, Nanjing, 211166, China. 2. Department of Gastroenterology, Dongtai People's Hospital, Yan Chen, 224000, Jiangsu, China. 3. Department of Oncology, The Second Affiliated Hospital, Nanjing Medical University, Nanjing, 211166, China. 4. Department of Medical Center for Digestive Diseases, The Second Affiliated Hospital, Nanjing Medical University, Nanjing, 211166, China. 15150543586@163.com. 5. Department of Digestive Diseases Kizilsu Kirghiz, The People's Hospital of Kizilsu Kirghiz Autonomous Prefecture, Kizilsu Kirghiz, 845350, China. 15150543586@163.com. 6. Department of Gastroenterology, Dongtai People's Hospital, Yan Chen, 224000, Jiangsu, China. 18921830588@189.cn. 7. Department of Medical Center for Digestive Diseases, The Second Affiliated Hospital, Nanjing Medical University, Nanjing, 211166, China. linmiao@njmu.edu.cn.
Abstract
PURPOSE: Cholangiocarcinoma (CCA) is the second most malignant tumor of the hepatobiliary system. Due to its cumbersome early diagnosis and rapid progression, chemotherapy has become the main treatment option. Primary drug resistance is a major cause of the poor efficacy of chemotherapeutic drugs. Therefore, it is considered urgent to explore new drugs to overcome primary drug resistance of CCA. METHODS: Western blot and qRT-PCR assays were used to assess the expression of myotrophin (MTPN) and microRNA-885-5p (miR-885-5p) in CCA tissues and cells. The viability of CCA cells treated with arsenic trioxide (ATO), 5-fluorouracil (5-Fu) and cisplatin (CDDP) was analyzed using a CCK-8 assay. A luciferase reporter assay was used to assess the interaction between miR-885-5p and MTPN. Kaplan-Meier analyses were used for survival assessments. RESULT: We found that ATO can reduce the resistance of CCA cells to 5-Fu and CDDP and promote the killing effect of 5-Fu and CDDP. Low-dose ATO showed an anti-drug-resistance effect through up-regulation of the expression of miR-885-5p. Combined with sequencing results and database predictions, we found that MTPN may serve as a direct target of miR-885-5p. After MTPN knockdown, the sensitivity of CCA cells to 5-FU and CDDP was increased. Finally, we found that ATO can reverse chemotherapy resistance induced by overexpression of MTPN. CONCLUSION: Our data indicate that the ATO/miR-885-5p/MTPN axis may serve as a target for improving the sensitivity of CCA cells to chemotherapy.
PURPOSE: Cholangiocarcinoma (CCA) is the second most malignant tumor of the hepatobiliary system. Due to its cumbersome early diagnosis and rapid progression, chemotherapy has become the main treatment option. Primary drug resistance is a major cause of the poor efficacy of chemotherapeutic drugs. Therefore, it is considered urgent to explore new drugs to overcome primary drug resistance of CCA. METHODS: Western blot and qRT-PCR assays were used to assess the expression of myotrophin (MTPN) and microRNA-885-5p (miR-885-5p) in CCA tissues and cells. The viability of CCA cells treated with arsenic trioxide (ATO), 5-fluorouracil (5-Fu) and cisplatin (CDDP) was analyzed using a CCK-8 assay. A luciferase reporter assay was used to assess the interaction between miR-885-5p and MTPN. Kaplan-Meier analyses were used for survival assessments. RESULT: We found that ATO can reduce the resistance of CCA cells to 5-Fu and CDDP and promote the killing effect of 5-Fu and CDDP. Low-dose ATO showed an anti-drug-resistance effect through up-regulation of the expression of miR-885-5p. Combined with sequencing results and database predictions, we found that MTPN may serve as a direct target of miR-885-5p. After MTPN knockdown, the sensitivity of CCA cells to 5-FU and CDDP was increased. Finally, we found that ATO can reverse chemotherapy resistance induced by overexpression of MTPN. CONCLUSION: Our data indicate that the ATO/miR-885-5p/MTPN axis may serve as a target for improving the sensitivity of CCA cells to chemotherapy.