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X 射线和 EGFR、PI3K/mTOR、Bcl-2 抑制剂对乳腺癌、肺癌和宫颈癌细胞的选择性治疗益处。

Selective therapeutic benefit of X-rays and inhibitors of EGFR, PI3K/mTOR, and Bcl-2 in breast, lung, and cervical cancer cells.

机构信息

Division of Radiobiology, Department of Medical Imaging and Clinical Oncology, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, 7505, South Africa.

Division of Radiobiology, Department of Medical Imaging and Clinical Oncology, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, 7505, South Africa.

出版信息

Eur J Pharmacol. 2021 Dec 5;912:174612. doi: 10.1016/j.ejphar.2021.174612. Epub 2021 Nov 2.

Abstract

Cancer continues to be a growing burden, especially in the resource limited regions of the world, and more effective and affordable therapies are highly desirable. In this study, the effect of X-ray irradiation and four inhibitors, viz. those against epidermal growth factor receptor (EGFR), phosphatidylinositol 3-kinase (PI3K), mammalian target of rapamycin (mTOR) and B-cell lymphoma 2 (Bcl-2) was evaluated in lung, breast, and cervical cancer cell lines, including normal cell lines to determine and compare the potential therapeutic benefit of these treatment modalities. A clonogenic survival assay was used to determine the radiosensitivity and cytotoxicity of inhibitors of EGFR, PI3K/mTOR, and Bcl-2 in the cell lines. From the data, the equivalent dose at which 50% of the cell populations were killed, for cancer and normal cells, was used to determine the relative cellular sensitivity to X-ray irradiation and inhibitor treatment. It was found that breast cancer cell lines were more sensitive to X-ray irradiation, whilst cervical and lung cancer cell lines were more sensitive to EGFR and PI3K/mTOR inhibitor therapy. These data suggest that patients with breast cancer possessing similar characteristics to MDA-MB-231 and MCF-7 cells may derive therapeutic benefit from X-ray irradiation, whilst EGFR and PI3K/mTOR inhibitor therapy may potentially benefit cancer patients possessing cancers similar to HeLa and A549 cells.

摘要

癌症仍然是一个不断增长的负担,特别是在世界资源有限的地区,因此更有效和负担得起的治疗方法是非常需要的。在这项研究中,评估了 X 射线照射和四种抑制剂(针对表皮生长因子受体 (EGFR)、磷脂酰肌醇 3-激酶 (PI3K)、雷帕霉素靶蛋白 (mTOR) 和 B 细胞淋巴瘤 2 (Bcl-2))对肺癌、乳腺癌和宫颈癌细胞系的影响,包括正常细胞系,以确定和比较这些治疗方式的潜在治疗益处。集落形成存活测定用于确定 EGFR、PI3K/mTOR 和 Bcl-2 抑制剂在细胞系中的放射敏感性和细胞毒性。根据数据,用于杀死 50%细胞群体的等效剂量用于确定细胞对 X 射线照射和抑制剂治疗的相对细胞敏感性。结果发现,乳腺癌细胞系对 X 射线照射更敏感,而宫颈和肺癌细胞系对 EGFR 和 PI3K/mTOR 抑制剂治疗更敏感。这些数据表明,具有类似于 MDA-MB-231 和 MCF-7 细胞特征的乳腺癌患者可能从 X 射线照射中获益,而 EGFR 和 PI3K/mTOR 抑制剂治疗可能对具有类似于 HeLa 和 A549 细胞的癌症的癌症患者有益。

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