Department of Pharmaceutics and Pharmaceutical Technology, Taif University, Taif, 21944, Saudi Arabia.
Department of Pharmaceutical Chemistry, College of Pharmacy, Taif University, P.O. Box 11099, Taif, 21944, Saudi Arabia.
Med Oncol. 2023 Jul 29;40(9):256. doi: 10.1007/s12032-023-02122-6.
Colorectal cancer (CRC), the third most common cancer in men and women, accounts for 8% of new cancer cases in the US and 8 to 9% of the nation's anticipated cancer mortality in 2014. In the pathophysiology of colon cancer, heat shock protein 70 (HSP70) and CXCR4 are essential. In this research, we concentrated on the connection between CXCR4 expression and HSP70 inhibitor activity in the development of colorectal cancer. The HSP70 inhibitor's effect on cell proliferation was also evaluated. Samples were obtained from patients with CRC; the surrounding marginal tissues were considered healthy. The One CRC cell lines (HCA-7) were divided into two groups based on untreated and treated with anti-HSP70. HSP70 and CXCR4 mRNA expression and migration (Wound healing assay) were measured in these groups. Also, we evaluated the expression levels of HSP70 and CXCR4 in thirty CRC and healthy non-cancerous samples (Using Real-time PCR and Western Blotting). Moreover, we examined the viability of CRC cells in untreated and treated groups with anti-HSP70. Higher expression levels of CXCR4 (p < 0.0001) and HSP70 (p = 0.002) mRNA were observed in patients who had CRC. In contrast, lower mRNA expressions of HSP70 (p < 0.0001) and CXCR4 (P < 0.0001) were detected in the CRC cell line (HCA-7) after being treated with anti-HSP70. Moreover, the viability and migration of cancer cells were remarkably reduced in CRC cells treated with anti-HSP70. Our study's innovation was the in vitro demonstration of inhibiting HSP70 in the CRC cancer cell line drastically reduced CXCR4 expression, viability, and cancer cell migration. These findings may pave the way for additional studies on CRC cancer treatment and be examined in vivo in studies, given that the primary goal of therapy is to decrease the viability and spread of cancer cells.
结直肠癌(CRC)是男性和女性中第三常见的癌症,占美国新癌症病例的 8%,也是 2014 年美国预计癌症死亡人数的 8%至 9%。在结肠癌的病理生理学中,热休克蛋白 70(HSP70)和 CXCR4 是必不可少的。在这项研究中,我们专注于 CXCR4 表达与 HSP70 抑制剂在结直肠癌发展中的活性之间的关系。还评估了 HSP70 抑制剂对细胞增殖的影响。从 CRC 患者中获取样本,将其周围边缘组织视为健康组织。将 One CRC 细胞系(HCA-7)分为未经处理和用抗 HSP70 处理的两组。在这些组中测量 HSP70 和 CXCR4 mRNA 的表达和迁移(伤口愈合测定)。此外,我们使用实时 PCR 和 Western Blotting 评估了 30 个 CRC 和健康非癌样本中 HSP70 和 CXCR4 的表达水平。此外,我们检查了未经处理和用抗 HSP70 处理的 CRC 细胞系的活力。在患有 CRC 的患者中观察到 CXCR4(p<0.0001)和 HSP70(p=0.002)mRNA 的表达水平更高。相比之下,在用抗 HSP70 处理后,CRC 细胞系(HCA-7)中 HSP70(p<0.0001)和 CXCR4(P<0.0001)的 mRNA 表达水平降低。此外,在 CRC 细胞中用抗 HSP70 处理后,癌细胞的活力和迁移明显降低。我们研究的创新之处在于,在 CRC 癌细胞系中体外抑制 HSP70 可显著降低 CXCR4 表达、活力和癌细胞迁移。鉴于治疗的主要目标是降低癌细胞的活力和扩散,这些发现可能为 CRC 癌症治疗的进一步研究铺平道路,并在体内研究中进行检验。