title: ASIC1a mediates the drug resistance of human hepatocellular carcinoma via the Ca2+/PI3-kinase/AKT signaling pathway.
abstract: Chemotherapy is the main treatment method of patients with advanced liver cancer. However, drug resistance is a serious problem in the treatment of hepatocellular carcinoma (HCC). Acid sensing ion channel 1a (ASIC1a) is a H+-gated cation channel; it mediates tumor cell migration and invasion, which suggests that it is involved in the development of malignant tumors. Therefore, we studied the relationship between ASIC1a and drug resistance in human hepatocellular carcinoma. In our study, we found that ASIC1a is highly expressed in human HCC tissue, and that its levels were significantly increased in resistant HCC cells Bel7402/FU and HepG2/ADM. Inhibiting the activity of ASIC1a enhances the chemosensitivity of Bel7402/FU and HepG2/ADM cells. The overexpression of ASIC1a contributed to drug resistance in Bel7402 and HepG2 cells, whereas knockdown of ASIC1a overcame drug resistance in Bel7402/FU and HepG2/ADM cells. We further demonstrated that ASIC1a mediated calcium influx, which resulted in the activation of PI3K/AKT signaling and increased drug resistance. These data suggest that ASIC1a/Ca2+/PI3K/AKT signaling represents a novel pathway that regulates drug resistance, thus offering a potential target for chemotherapy of HCC.
authors.affiliation: School of Pharmacy, Anhui Medical University, Hefei, China.
authors.forename: Yihao
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Anhui Medical University, Hefei, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Anhui Medical University, Hefei, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Wu
authors.affiliation: The First Affiliated Hospital of Anhui Medical University, Hefei, China.|Third-Grade Pharmaceutical Chemistry Laboratory of State Administration of Traditional Chinese Medicine, Hefei, Anhui, China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Xia
authors.affiliation: School of Pharmacy, Anhui Medical University, Hefei, China.|The First Affiliated Hospital of Anhui Medical University, Hefei, China.|Third-Grade Pharmaceutical Chemistry Laboratory of State Administration of Traditional Chinese Medicine, Hefei, Anhui, China.
authors.forename: Dujuan
authors.initials: D
authors.lastname: Xu
mesh_terms: D062565:Acid Sensing Ion Channels / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D056945:Hep G2 Cells; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034622:RNA Interference; D015398:Signal Transduction
chemical_list: C568266:ASIC1 protein, human; D062565:Acid Sensing Ion Channels; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D002118:Calcium