溶酶体相关膜蛋白3通过VEGF/AKT通路抑制PC-3细胞增殖、转移及血管生成  

LAMP3 inhibited the proliferation,metastatic and PC⁃3⁃induced vasculogenesis of HUVEC by regulating VEGF/AKT signaling

作　　者：陈灿伟 廖壮文[1] 范子文[1] 黄帅 黄彦[1] 陈斌伟[1] CHEN Canwei;LIAO Zhuangwen;FAN Ziwen;HUANG Shuai;HUANG Yan;CHEN Binwei(Department of Orthopedics,the Second Affiliated Hospital of Guangzhou Medical University,Guangzhou 510260,China)

机构地区：[1]广州医科大学附属第二医院骨科,广州510260

出　　处：《实用医学杂志》2024年第2期182-187,共6页The Journal of Practical Medicine

基　　金：广东省自然科学基金面上项目(编号:2019A1515010690);广州市科技计划项目(编号:202002030014)。

摘　　要：目的探索LAMP3对PC-3细胞增殖、迁移及血管生成的影响。方法Western blot(WB)及RT-PCR检测LAMP3在正常前列腺上皮细胞及前列腺癌骨转移细胞中的表达。构建稳定沉默LAMP3的PC-3细胞,分别使用CCK8、划痕试验、Transwell试验检测LAMP3对PC-3细胞增殖、迁移与侵袭的影响。通过ELISA及血管生成试验检测血管内皮生长因子VEGF、基质金属酶MMP9的表达及HUVEC细胞的血管生成,最后使用WB及RT-PCR检测VEGF、AKT/p-AKT的表达。结果LAMP3在前列腺癌细胞中的表达较正常前列腺上皮细胞明显升高,以PC-3细胞最明显(P<0.05)。沉默LAMP3能抑制PC-3细胞的增殖、迁移与侵袭能力,同时能抑制VEGF、MMP9的表达及PC-3细胞诱导的血管生成,差异有统计学意义(P<0.05)。此外,LAMP3能下调PC-3细胞中VEGF、AKT/p-AKT的表达。结论LAMP3能通过调控VEGF/AKT通路影响PC-3细胞的增殖、转移和血管生成,LAMP3可能是前列腺癌骨转移的潜在治疗靶点之一。Objective To explore the impactof Lysosome⁃Associated Membrane Protein 3(LAMP3)on theproliferation,migration and angiogenesis of PC⁃3 cells.Methods LAMP3 expression in normal prostate epithelial cells and prostate cancer bone metastasis cells was detected using western blot and RT⁃PCR.Stable LAMP3⁃silenced PC⁃3 cells were constructed,and the effects of LAMP3 on proliferation,invasion,and migration of PC⁃3 cells were assessed using CCK8,scratch assay,and transwell assay,respectively.ELISA and angiogenesis assays were employed to examine the expression of VEGF and MMP9,as well as angiogenesis of HUVEC cells induced by PC⁃3 cells.Finally,WB and RT⁃PCR were used to detect the expression of VEGF,AKT/p⁃AKT.Results Our findings showed that the expression level of LAMP3 was significantly higherin prostate cellsthan in normal prostate epithelial cells,especially in PC⁃3 cells(P<0.05).We also found that silencing LAMP3 could inhibit the proliferation,migration and invasion of PC⁃3 cells,along with the expression of VEGF and MMP9 and the PC⁃3 cells⁃induced angiogenesis,and these results were statistically significant(P<0.05).Furthermore,LAMP3 downregulated the expression of VEGF and AKT/p⁃AKT in PC⁃3 cells.Conclusion LAMP3 can affect the proliferation,migrationand angiogenesis of PC⁃3 cells through the regulation of VEGF/AKT pathway.Thus,LAMP3 might be a potential thera⁃peutic target for prostate cancer bone metastasis.

关 键 词：溶酶体相关膜蛋白3 前列腺癌 骨转移 血管内皮生长因子 血管生成 

分 类 号：R737.25[医药卫生—肿瘤]