在胰腺癌中敲低 有助于缓解吉西他滨耐药性。
Knockdown of in Pancreatic Cancer Helps Ameliorate Gemcitabine Resistance.
机构信息
Department of Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 250021 Jinan, Shandong, China.
Liver Gall Bladder and Pancreatic Surgery Ward, Qinghai Red Cross Hospital, 810001 Xining, Qinghai, China.
出版信息
Front Biosci (Landmark Ed). 2024 Jul 25;29(7):269. doi: 10.31083/j.fbl2907269.
BACKGROUND
The gene is a gemcitabine (GEM) resistance gene; however, the mechanism by which it regulates GEM resistance in pancreatic cancer remains unclear.
METHODS
The cell line was treated with GEM and then stimulated with . Subsequently, we constructed GEM-resistant pancreatic cancer cell lines, knocked down in these cell lines, and detected changes in the proliferation and apoptosis of drug-resistant cancer cells. In addition, the protein expression levels of , , and were determined. The xenograft tumor models of nude mice were constructed by subcutaneously injecting GEM-resistant cells into mouse axilla. The tumors were removed, dissected, and weighed after 6 weeks. The protein levels of , , and in tumor tissues were quantified. In addition, the percentage of M2 macrophages in tumor tissues was determined using flow cytometry.
RESULTS
The protein levels of in pancreatic cancer cells were significantly decreased after GEM treatment. The protein expression of was downregulated, whereas the expressions of and were upregulated after stimulation. Apoptosis increased and proliferation decreased after knockdown in GEM-resistant pancreatic cancer cells, moreover, silencing promoted the expression of Caspase 3 and Cleaved caspase 3. In addition, the protein expression of was upregulated, whereas the expressions of and were downregulated. Further, the volume and weight of the transplanted tumor decreased after knockdown. The protein expression of was upregulated, whereas the expressions of and were downregulated in tumor tissues. In addition, the percentage of M2 macrophages decreased in tumor tissues after knockdown.
CONCLUSIONS
The knockdown of inhibits epithelial-to-mesenchymal transition, suppresses the proliferation and promotes the apoptosis of drug-resistant cancer cells, and decreases the macrophage polarization to the M2 phenotype, consequently ameliorating GEM resistance in pancreatic cancer.
背景
基因是吉西他滨（GEM）耐药基因；然而，其调节胰腺癌 GEM 耐药的机制尚不清楚。
方法
用 GEM 处理 细胞系，然后用 刺激。随后，我们构建了 GEM 耐药的胰腺癌细胞系，在这些细胞系中敲低 ，并检测耐药癌细胞增殖和凋亡的变化。此外，还测定了 、 、 蛋白的表达水平。将 GEM 耐药的 细胞通过皮下注射到小鼠腋窝中构建裸鼠异种移植肿瘤模型。6 周后取出肿瘤，解剖并称重。定量肿瘤组织中 、 、 的蛋白水平。此外，使用流式细胞术测定肿瘤组织中 M2 巨噬细胞的百分比。
结果
GEM 处理后胰腺癌细胞中 的蛋白水平显著降低。 刺激后， 的蛋白表达下调， 、 的表达上调。GEM 耐药的胰腺癌细胞中 敲低后，细胞凋亡增加，增殖减少，并且沉默 促进 Caspase 3 和 Cleaved caspase 3 的表达。此外， 的蛋白表达上调， 、 的表达下调。进一步， 敲低后移植瘤的体积和重量减小。肿瘤组织中 的蛋白表达上调， 、 的表达下调。此外， 敲低后肿瘤组织中 M2 巨噬细胞的百分比降低。
结论
敲低抑制上皮间质转化，抑制耐药癌细胞的增殖并促进其凋亡，并减少巨噬细胞向 M2 表型的极化，从而改善胰腺癌中的 GEM 耐药性。
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