Heat shock protein 70-2 (HSP70-2) is a novel therapeutic target for colorectal cancer and is associated with tumor growth.
Heat shock protein 70-2 (HSP70-2) is a novel therapeutic target for colorectal cancer and is associated with tumor growth.
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DOI：
10.1186/s12885-016-2592-7
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发表时间：
2016-07-29
期刊：
影响因子：
3.8
通讯作者：
Suri A
中科院分区：
文献类型：
--
作者：
Jagadish N;Parashar D;Gupta N;Agarwal S;Suri V;Kumar R;Suri V;Sadasukhi TC;Gupta A;Ansari AS;Lohiya NK;Suri A
结直肠癌 (CRC) 是全球男性和女性癌症相关死亡的第三大原因。我们最近的研究表明热休克蛋白 70-2 (HSP70-2) 与膀胱尿路上皮癌存在关联。在本研究中，我们研究了临床标本中HSP70-2与结直肠癌细胞的各种恶性特性以及CRC的临床病理特征的关联。通过 RT-PCR、免疫组织化学、免疫荧光、流式细胞术和蛋白质印迹法研究 CRC 临床标本以及 COLO205 和 HCT116 细胞系中 HSP70-2 mRNA 和蛋白的表达。采用基于质粒的基因沉默方法在体外研究HSP70-2与COLO205和HCT116细胞的各种恶性特性以及在体内COLO205人异种移植小鼠模型中的肿瘤进展的关联。通过 RT-PCR 和 IHC，无论各个阶段和级别，78% 的 CRC 患者均检测到 HSP70-2 表达。我们的分析进一步表明，在 COLO205 和 HCT116 细胞系中均检测到 HSP70-2 表达。 HSP70-2表达的消除导致CRC细胞的细胞生长、集落形成能力、迁移和侵袭能力降低。此外，在体内小鼠模型中，HSP70-2表达的消除显示COLO205人异种移植物中肿瘤生长显着减少。总的来说，我们的结果表明 HSP70-2 与 CRC 临床标本相关。此外，HSP70-2表达的下调可减少细胞增殖和肿瘤生长，表明HSP70-2可能是CRC治疗的潜在治疗靶点。
Colorectal cancer (CRC) is the third leading cause of cancer related deaths worldwide both in men and women. Our recent studies have indicated an association of heat shock protein 70–2 (HSP70-2) with bladder urothelial carcinoma. In the present study, we investigated the association of HSP70-2 with various malignant properties of colorectal cancer cells and clinic-pathological features of CRC in clinical specimens. HSP70-2 mRNA and protein was investigated expression by RT-PCR, immunohistochemistry, immunofluorescence, flow cytometry and Western blotting in CRC clinical specimens and COLO205 and HCT116 cell lines. Plasmid-based gene silencing approach was employed to study the association of HSP70-2 with various malignant properties of COLO205 and HCT116 cells in in vitro and with tumor progression in in vivo COLO205 human xenograft mice model. HSP70-2 expression was detected in 78 % of CRC patients irrespective of various stages and grades by RT-PCR and IHC. Our analysis further revealed that HSP70-2 expression was detected in both COLO205 and HCT116 cell lines. Ablation of HSP70-2 expression resulted in reduced cellular growth, colony forming ability, migratory and invasive ability of CRC cells. In addition, ablation of HSP70-2 expression showed significant reduction in tumor growth in COLO205 human xenograft in in vivo mouse model. Collectively, our results indicate that HSP70-2 is associated with CRC clinical specimens. In addition, down regulation of HSP70-2 expression reduces cellular proliferation and tumor growth indicating that HSP70-2 may be a potential therapeutic target for CRC treatment.