title: RLIP76 increases apoptosis through Akt/mTOR signaling pathway in gastric cancer.
abstract: RLIP76 is a stress-responsive multifunctional protein and is usually overexpressed in malignant carcinomas. It plays a significant role in multiple cellular biological behaviors, including cell growth, motility, division and apoptosis, in many types of malignant cells. However, functions of RLIP76 in gastric cancer (GC) remain unknown. In the present study, RLIP76 was overexpressed in GC tissues by immunohistochemistry. RLIP76-targeted shRNA-containing lentivirus (KD) and the scrambled shRNA (NC) were used to explore the knockout of RLIP76 on cellular functions of human GC SGC-7901 and MGC-803 cells. Quantitative RT-PCR and western blotting were used to confirm that the RLIP76 was suppressed both on mRNA and protein levels after transfection. The mRNA level in SGC-7901 and MGC-803 after transfection of RLIP76-targeted shRNA was 0.245722±0.021077 (p<0.05) and 0.225389±0.00974 (p<0.05), respectively. Our results showed that the konckdown of RLIP76 downregulated cell growth after 24 h in Cell Counting Kit-8 (CCK-8) assay, reduced migration from 486.7±128.8 to 219.7±43.6 in SGC-7901 (p<0.05) and from 630±95 to 333.7±46.5 in MGC-803 (p<0.05), decreased invasion from 306±33.5 to 97.7±24.3 in SGC-7901 (p<0.05) and from 350±50.9 to 163.3±87.5 in MGC-803 (p<0.05). Length of vascular endothelial growth factor (VEGF)-induced tube formation also decreased from 202.8±83.3 to 44.5±3.69 in SGC-7901 and from 193±3.5 to 71.8±8.83 in MGC-803 (p<0.05). Phosphorylation level of Akt declined from 138.45±13.8 to 69.9±29.7% in SGC-7901, and from 115.5±26.6 to 49.07±27% in MGC-803 (p<0.05) and phosphorylation level of mTOR also significantly decreased (p<0.05). While apoptosis of GC cells increased which we verified with apoptosis proteins and staining analysis. Our data showed that RLIP76 plays a significant oncogenic role in GC and it maybe a potential target in GC treatment.
authors: Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors: Wenwen
authors: W
authors: Wang
authors: Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors: Juan
authors: J
authors: Liu
authors: Central Laboratory, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors: Jianni
authors: J
authors: Qi
authors: Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors: Junyong
authors: J
authors: Zhang
authors: Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors: Qiang
authors: Q
authors: Zhu
authors: Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors: Chengyong
authors: C
authors: Qin
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis / Q000235:genetics*; D017209:Apoptosis / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D020690:GTPase-Activating Proteins / Q000096:biosynthesis / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D051058:Oncogene Protein v-akt / Q000235:genetics*; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D058570:TOR Serine-Threonine Kinases / Q000235:genetics*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
chemical_list: D018528:ATP-Binding Cassette Transporters; D014408:Biomarkers, Tumor; D020690:GTPase-Activating Proteins; C095637:RALBP1 protein, human; D034741:RNA, Small Interfering; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C546842:MTOR protein, human; D051058:Oncogene Protein v-akt; D058570:TOR Serine-Threonine Kinases