中国癌症杂志
中國癌癥雜誌
중국암증잡지
CHINA ONCOLOGY
2014年
10期
770-776
,共7页
MDA-MB-231/Gem%趋化因子配基1%mTOR%乳腺癌
MDA-MB-231/Gem%趨化因子配基1%mTOR%乳腺癌
MDA-MB-231/Gem%추화인자배기1%mTOR%유선암
MDA-MB-231/Gem%C chemokine ligand 1%mTOR%Breast cancer
背景与目的：统计表明90%以上肿瘤患者的死亡与肿瘤耐药相关，而在乳腺癌中常见PI3K/Akt/mTOR信号通路的异常激活，以此通路为靶点的药物已成为乳腺癌治疗的研究热点。本研究主要分析C族趋化因子配基1(C chemokine ligand 1，XCL1)对乳腺癌耐药细胞增殖的影响及其产生机制。方法：建立吉西他滨耐药性人乳腺癌细胞系MDA-MB-231/Gem。采用CCK8检测MDA-MB-231和MDA-MB-231/Gem的增殖能力，RT-PCR、ELISA检测2株细胞株XCL1表达差异，Western blot检测mTOR的表达。结果：与MDA-MB-231相比，MDA-MB-231/Gem的增殖能力增强，XCL1在耐药细胞株表达增强。mTOR在耐药细胞株表达水平及磷酸化水平增强。在MDA-MB-231中加入外源性XCL124 h后，细胞增殖能力增强。而在MDA-MB-231/Gem中加入抗XCL1抗体后，细胞增殖能力降低。mTOR抑制剂处理MDA-MB-231/Gem后，细胞增殖能力降低，XCL1产生减少。结论：趋化因子XCL1的分泌可促进乳腺癌耐药细胞的增殖并由mTOR信号通路介导产生。
揹景與目的：統計錶明90%以上腫瘤患者的死亡與腫瘤耐藥相關，而在乳腺癌中常見PI3K/Akt/mTOR信號通路的異常激活，以此通路為靶點的藥物已成為乳腺癌治療的研究熱點。本研究主要分析C族趨化因子配基1(C chemokine ligand 1，XCL1)對乳腺癌耐藥細胞增殖的影響及其產生機製。方法：建立吉西他濱耐藥性人乳腺癌細胞繫MDA-MB-231/Gem。採用CCK8檢測MDA-MB-231和MDA-MB-231/Gem的增殖能力，RT-PCR、ELISA檢測2株細胞株XCL1錶達差異，Western blot檢測mTOR的錶達。結果：與MDA-MB-231相比，MDA-MB-231/Gem的增殖能力增彊，XCL1在耐藥細胞株錶達增彊。mTOR在耐藥細胞株錶達水平及燐痠化水平增彊。在MDA-MB-231中加入外源性XCL124 h後，細胞增殖能力增彊。而在MDA-MB-231/Gem中加入抗XCL1抗體後，細胞增殖能力降低。mTOR抑製劑處理MDA-MB-231/Gem後，細胞增殖能力降低，XCL1產生減少。結論：趨化因子XCL1的分泌可促進乳腺癌耐藥細胞的增殖併由mTOR信號通路介導產生。
배경여목적：통계표명90%이상종류환자적사망여종류내약상관，이재유선암중상견PI3K/Akt/mTOR신호통로적이상격활，이차통로위파점적약물이성위유선암치료적연구열점。본연구주요분석C족추화인자배기1(C chemokine ligand 1，XCL1)대유선암내약세포증식적영향급기산생궤제。방법：건립길서타빈내약성인유선암세포계MDA-MB-231/Gem。채용CCK8검측MDA-MB-231화MDA-MB-231/Gem적증식능력，RT-PCR、ELISA검측2주세포주XCL1표체차이，Western blot검측mTOR적표체。결과：여MDA-MB-231상비，MDA-MB-231/Gem적증식능력증강，XCL1재내약세포주표체증강。mTOR재내약세포주표체수평급린산화수평증강。재MDA-MB-231중가입외원성XCL124 h후，세포증식능력증강。이재MDA-MB-231/Gem중가입항XCL1항체후，세포증식능력강저。mTOR억제제처리MDA-MB-231/Gem후，세포증식능력강저，XCL1산생감소。결론：추화인자XCL1적분비가촉진유선암내약세포적증식병유mTOR신호통로개도산생。
Background and purpose: More than 90% of cancer patients are incurable because of drug resistance. Activation of PI3K/Akt/mTOR signaling pathway in breast cancer, as a target for chemotherapy drugs has become a hot topic of breast cancer treatment. This study aimed to investigate the effect and mechanism of XCL1 on the proliferation of drug-resistant breast cancer cell, whether is related with the mTOR signaling pathway. Methods:Established gemcitabine-resistant breast cancer cell lines (MDA-MB-231/Gem). CCK8 to detect the proliferation of MDA-MB-231 and MDA-MB-231/Gem, RT-PCR and ELISA to determine the XCL1 expression level of the two cell lines, Western blot to detect the expression of mTOR. Results:Compared with MDA-MB-231, MDA-MB-231/Gem showed an enhanced proliferative capacity. The expression of XCL1 was increased in the resistant cell lines. Both of protein level and phosphorylation level of mTOR increased in drug-resistant cell lines. The MDA-MB-231 added exogenous XCL1 for 24 h, showed an enhanced cell proliferation. Adding anti-XCL1 antibodies in MDA-MB-231/Gem could reduce cell proliferation and treating MDA-MB-231/Gem with the mTOR inhibitor could also reduce cell proliferation, as well as the XCL1 expression level. Conclusion:XCL1 promotes the proliferation of drug-resistant breast cancer cells mediated by activation of the mTOR pathway.
