title: Decreased LRIG1 in Human Ovarian Cancer Cell SKOV3 Upregulates MRP-1 and Contributes to the Chemoresistance of VP16.
abstract: The leucine-rich repeats and immunoglobulin-like domains (LRIG) are used as tumor suppressors in clinical applications. Although the LRIG has been identified to manipulate the cell proliferation via various oncogenic receptor tyrosine kinases in diverse cancers, its role in multidrug resistance needs to be further elucidated, especially in human ovarian cancer. We herein established that the etoposide (VP16)-resistant SKOV3 human ovarian cancer cell clones (SKOV3/VP16 cells) and mRNA expression of LRIG1 were significantly reduced by the treatment of VP16 in a concentration-dependent manner. Moreover, downregulated LRIG1 in SKOV3 could enhance the colony formation and resist the inhibition of proliferation by VP16, leading to the elevated expression of Bcl-2 and decreased apoptosis of SKOV3. Interestingly, our results uncovered that the multidrug resistance-associated protein 1 (MRP-1) was upregulated for the chemoresistance of VP16. To overcome the chemoresistance of SKOV3, SKOV3/VP16 was ectopically expressed of LRIG1. We found that the inhibition of VP16 on colony formation and proliferation was remarkably enhanced with increased apoptosis in SKOV3/VP16. Furthermore, the expression of MRP-1 and Bcl-2 was also inhibited, suggesting that the LRIG1could negatively control MRP-1 and the apoptosis to improve the sensitivity of VP16-related chemotherapy.
authors.affiliation: 1 Department of Gynaecology, The Second Affiliated Hospital of Guilin Medical University , Guilin, China .
authors.forename: Hua
authors.initials: H
authors.lastname: Yang
authors.affiliation: 2 Department of Gynaecology, The Affiliated Hospital of Guilin Medical University , Guilin, China .
authors.forename: Jun
authors.initials: J
authors.lastname: Yao
authors.affiliation: 2 Department of Gynaecology, The Affiliated Hospital of Guilin Medical University , Guilin, China .
authors.forename: Jiangpin
authors.initials: J
authors.lastname: Yin
authors.affiliation: 1 Department of Gynaecology, The Second Affiliated Hospital of Guilin Medical University , Guilin, China .
authors.forename: Xuan
authors.initials: X
authors.lastname: Wei
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D005047:Etoposide / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D005047:Etoposide; D008562:Membrane Glycoproteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C484445:LRIG1 protein, human; C421109:multidrug resistance-associated protein 1
keywords: LRIG1; MRP-1; chemoresistance; ovarian cancer