Knockdown of TGF-β in Pancreatic Cancer Helps Ameliorate Gemcitabine Resistance.

Autor:	Wang X; Department of Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 250021 Jinan, Shandong, China., Su W; Liver Gall Bladder and Pancreatic Surgery Ward, Qinghai Red Cross Hospital, 810001 Xining, Qinghai, China., Qin C; Department of Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 250021 Jinan, Shandong, China., Gao R; Department of Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 250021 Jinan, Shandong, China., Shao S; Department of Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 250021 Jinan, Shandong, China., Xu X; Department of Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 250021 Jinan, Shandong, China., Zhang Z; Department of Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 250021 Jinan, Shandong, China., Gao J; Liver Gall Bladder and Pancreatic Surgery Ward, Qinghai Red Cross Hospital, 810001 Xining, Qinghai, China.
Jazyk:	angličtina
Zdroj:	Frontiers in bioscience (Landmark edition) [Front Biosci (Landmark Ed)] 2024 Jul 25; Vol. 29 (7), pp. 269.
DOI:	10.31083/j.fbl2907269
Abstrakt:	Background: The TGF-β gene is a gemcitabine (GEM) resistance gene; however, the mechanism by which it regulates GEM resistance in pancreatic cancer remains unclear. Methods: The PANC-1 cell line was treated with GEM and then stimulated with TGF-β . Subsequently, we constructed GEM-resistant pancreatic cancer cell lines, knocked down TGF-β in these cell lines, and detected changes in the proliferation and apoptosis of drug-resistant cancer cells. In addition, the protein expression levels of KLF-4 , GFI-1 , and ZEB-1 were determined. The xenograft tumor models of nude mice were constructed by subcutaneously injecting GEM-resistant PANC-1 cells into mouse axilla. The tumors were removed, dissected, and weighed after 6 weeks. The protein levels of KLF-4 , GFI-1 , and ZEB-1 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 TGF-β in pancreatic cancer cells were significantly decreased after GEM treatment. The protein expression of KLF-4 was downregulated, whereas the expressions of GFI-1 and ZEB-1 were upregulated after TGF-β stimulation. Apoptosis increased and proliferation decreased after TGF-β knockdown in GEM-resistant pancreatic cancer cells, moreover, silencing TGF-β promoted the expression of Caspase 3 and Cleaved caspase 3. In addition, the protein expression of KLF-4 was upregulated, whereas the expressions of GFI-1 and ZEB-1 were downregulated. Further, the volume and weight of the transplanted tumor decreased after TGF-β knockdown. The protein expression of KLF-4 was upregulated, whereas the expressions of GFI-1 and ZEB-1 were downregulated in tumor tissues. In addition, the percentage of M2 macrophages decreased in tumor tissues after TGF-β knockdown. Conclusions: The knockdown of TGF-β 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. Competing Interests: The authors declare no conflict of interest. (© 2024 The Author(s). Published by IMR Press.)
Databáze:	MEDLINE
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