LRRC3B在非小细胞肺癌中下调并与肺癌细胞增殖和侵袭能力相关

摘要

Background and objective LRRC3B expression is downregulated in many kinds of malignant tumors and it is regarded as tumor inhibition protein. However, the expression pattern and biological effect are still unclear in non-small cell lung cancer (NSCLC). Study of human cancer microarray showed LRRC3B was downregulated in breast cancer and colorectal cancer, which declares that LRRC3B takes part in tumor formation. hTis study is to investigate the expression of LRRC3B in lung cancer cell lines and the inlfuence of LRRC3B during cell proliferation, invasion and cell cycle. Methods hTe expression of LRRC3B was detected through Western blot and Realtime RT-PCR. MTT assay, colony formation assay and matrigel invasion assay were performed to explore the effect of LRRC3B on cell proliferation, invasion and cell cycle. LRRC3B siARN was transfected in lung cancer cell line H3255, and then the effect of LRRC3B on cell proliferation, invasion and cell cycle was analyzed. Results During 4 of 9 lung cancer cell lines, the expression of LRRC3B is downregulated compared with normal epithelial cells. Cell proliferation and invasion were inhibited in A549 and H460 atfer LRRC3B transfected. LRRC3B suppressed the progress of cell cycle and downregulated the expression of cyclin D1 and MMP9. hTe activity of proliferation and invasion was promoted atfer LRRC3B was knocked out in H3255. Conclusion LRRC3B expression downreguated in lung cancer cell lines and LRRC3B could inhibit lung cancer cell proliferation, invasion and cell cycle progress. LRRC3B could be a new target for lung cancer therapy.%背景与目的已有的研究表明：在许多恶性肿瘤细胞中，LRRC3B表达显著下调，被视为肿瘤抑制蛋白。然而，在非小细胞肺癌中它的表达模式和生物学作用缺乏研究。人类癌症微阵列的研究显示LR-RC3B在乳腺癌和结肠直肠癌表达下调，提示LRRC3B参与致癌作用。本研究的目的是研究LRRC3B在非小细胞肺癌中的必到状态及其与肺癌增殖、侵袭和细胞周期间的相关性，探讨LRRC3B在调控肺癌细胞增殖、侵袭及细胞周期中的作用。方法应用Western blot和Realtime RT-PCR检测LRRC3B在几株肺癌细胞系中的mRNA和蛋白表达水平。应用MTT法检测对转染LRRC3B的A549和H460细胞系细胞增殖能力变化，应用集落形成实验以及细胞侵袭实验研究LRRC3B对细胞增殖和侵袭以及细胞周期进程的作用。肺癌细胞系H3255中转染LR-RC3B siRAN验证LRRC3B对细胞的增殖以及侵袭能力和对细胞周期进程的影响。结果与正常NHBE细胞系相比，NSCLC细胞系中LRRC3B蛋白表达量显著下调，特别是H460、H358、HCC827以及A549。A549和H460细胞系转染LRRC3B后，细胞增殖和侵袭能力受到抑制。LRRC3B抑制细胞周期进程，并下调cyclin D1和MMP9的表达。H3255细胞中敲除LRRC3B，细胞增殖和侵袭能力显著增强，同时与细胞周期及侵袭能力相关的蛋白cyclin D1和MMP9表达略微上调。结论 LRRC3B在肺癌细胞系中表达下调，而上调LRRC3B则能够抑制肺癌细胞增殖和侵袭能力，并抑制细胞周期进程，可能是未来肺癌治疗的一个新靶点。