Department of Biochemistry, Faculty of Medical Sciences in Katowice, Medical University of Silesia, Medyków 18, 40-752 Katowice, Poland.
Int J Mol Sci. 2020 Nov 26;21(23):8976. doi: 10.3390/ijms21238976.
The strong association between diabetes mellitus type 2 and cancer is observed. The incidence of both diseases is increasing globally due to the interaction between them. Recent studies suggest that there is also an association between cancer incidence and anti-diabetic medications. An inhibitor of dipeptidyl-peptidase 4 (DPP-4), sitagliptin, is used in diabetes treatment. We examined the influence of sitagliptin alone or in combination with a cytostatic drug (paclitaxel) on the development of epithelial ovarian cancer cells and the process of metastasis. We examined migration, invasiveness, apoptosis, and metalloproteinases (MMPs) and their inhibitors' (TIMPs) production in two human ovarian cancer cell lines. Sitagliptin induced apoptosis by caspase 3/7 activation in paclitaxel-treated SKOV-3 and OVCAR-3 cells. Sitagliptin maintained paclitaxel influence on ERK and Akt signaling pathways. Sitagliptin additionally reduced migration and invasiveness of SKOV-3 cells. There were distinct differences of metalloproteinases production in sitagliptin-stimulated ovarian cancer cells in both cell lines, despite their identical histological classification. Only the SKOV-3 cell line expressed MMPs and TIMPs. SKOV-3 cells co-treated with sitagliptin and paclitaxel decreased concentrations of MMP-1, MMP-2, MMP-7, MMP-10, TIMP-1, TIMP-2. The obtained data showed that sitagliptin used with paclitaxel may be considered as a possibility of pharmacological modulation of intracellular transmission pathways to improve the response to chemotherapy.
2 型糖尿病与癌症之间存在强烈关联。由于两者之间的相互作用，这两种疾病的发病率在全球范围内都呈上升趋势。最近的研究表明，癌症发病率与抗糖尿病药物之间也存在关联。二肽基肽酶 4（DPP-4）抑制剂西他列汀用于治疗糖尿病。我们研究了西他列汀单独或与细胞毒性药物（紫杉醇）联合使用对上皮性卵巢癌细胞发展和转移过程的影响。我们检查了两种人卵巢癌细胞系中迁移、侵袭、细胞凋亡以及金属蛋白酶（MMPs）及其抑制剂（TIMPs）产生的变化。西他列汀通过 caspase 3/7 的激活诱导紫杉醇处理的 SKOV-3 和 OVCAR-3 细胞发生细胞凋亡。西他列汀维持了紫杉醇对 ERK 和 Akt 信号通路的影响。西他列汀还降低了 SKOV-3 细胞的迁移和侵袭能力。尽管两种细胞系的组织学分类相同，但在西他列汀刺激的卵巢癌细胞中 MMPs 的产生存在明显差异。只有 SKOV-3 细胞系表达 MMPs 和 TIMPs。用西他列汀和紫杉醇共同处理 SKOV-3 细胞会降低 MMP-1、MMP-2、MMP-7、MMP-10、TIMP-1 和 TIMP-2 的浓度。所得数据表明，与紫杉醇联合使用西他列汀可被视为调节细胞内转导途径以改善化疗反应的一种可能的药理学方法。
