| Haiyan Peng,Wenhua Zhao,Cuiyun Su,Xiangqun Song,Aiping Zeng,Huilin Wang,Ruiling Ning,Shaozhang Zhou. Role of the STAT3/survivin signaling pathway in the EML4-ALK-positive lung adenocarcinoma cell line H2228 before and after crizotinib-induced resistance. Oncol Transl Med, 2015, 1: 73-77. |
| Role of the STAT3/survivin signaling pathway in the EML4-ALK-positive lung adenocarcinoma cell line H2228 before and after crizotinib-induced resistance |
| Received:December 16, 2014 Revised:April 03, 2015 |
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| KeyWord:EML4-ALK fusion gene; H2228 cell line; crizotinib; apoptosis; STAT3/survivin signaling pathway |
| Author Name | Affiliation | E-mail | | Haiyan Peng | Guangxi Medical University | 784951431@qq.com | | Wenhua Zhao | Affiliated Cancer Hospital, Guangxi Medical University, Guangxi, China | 315333096@qq.com | | Cuiyun Su | Affiliated Cancer Hospital, Guangxi Medical University, Guangxi, China | | | Xiangqun Song | Affiliated Cancer Hospital, Guangxi Medical University, Guangxi, China | | | Aiping Zeng | Affiliated Cancer Hospital, Guangxi Medical University, Guangxi, China | | | Huilin Wang | Affiliated Cancer Hospital, Guangxi Medical University, Guangxi, China | | | Ruiling Ning | Affiliated Cancer Hospital, Guangxi Medical University, Guangxi, China | | | Shaozhang Zhou | Affiliated Cancer Hospital, Guangxi Medical University, Guangxi, China | zhoushaozhang@qq.com |
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| Abstract: |
| Objective This study investigated the role of the STAT3/survivin signaling pathway in the EML4-ALK–positive lung adenocarcinoma cell line H2228 before and after crizotinib-induced resistance. The mechanism
of resistance was studied. Methods Cell viability was determined using the MTT assay. Crizotinib-induced apoptosis in H2228 and H2228 crizotinib-resistant cells treated with the indicated doses of crizotinib was measured at different times (24 h, 48 h, 72 h) using flow cytometry. The levels of p-ALK, ALK, p-STAT3, STAT3, and survivin after treatment of cells with 0, 0.3, and 1 μM crizotinib for 72 h were determined using Western blot analysis. DNA sequencing was used to identify mutations in H2228 crizotinib-resistant cells. Results The crizotinib IC50 values in H2228 and H2228 crizotinib-resistant cells at 72 h were 334.5 nM and 3418 nM, respectively. The resistance index of H2228 crizotinib-resistant cells was 10.20. Crizotinib induced apoptosis in H2228 cells and reduced the levels of p-ALK, p-STAT3, and survivin. In contrast, no changes in the levels of p-ALK, p-STAT3, and survivin were observed in H2228 crizotinib-resistant cells. The mutations 2067G→A and 2182G→C in EML4-ALK were present in the H2228 crizotinib-resistant cells. Conclusion Crizotinib decreased the viability of H2228 cells in a dose- and time-dependent manner. In the STAT3/survivin pathway, downregulation of p-ALK, p-STAT3, and survivin might contribute to crizotinib-induced apoptosis in H2228 cells. However, the STAT3/survivin pathway in H2228 crizotinib-resistant cells was unaffected by crizotinib treatment. Acquired resistance in H2228 cells might be related to ALK mutations. |
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