The Role of Pioglitazone Against Ehrlich Solid Carcinoma Mice Model Through Antiproliferative and Antiangiogenic Pathways
The Role of Pioglitazone Against Ehrlich Solid Carcinoma Mice Model Through Antiproliferative and Antiangiogenic Pathways
Dalia Zaafar1*, Heba M.A Khalil2, Soha Hassanin3, Mohamed R. Mousa4, Mona G. Khalil1
ABSTRACT
Background: Cancer is one of the leading causes of death and morbidity worldwide, and it is linked to a variety of genetic and hormonal factors. Patients frequently experience cancer metastasis, relapse, and therapeutic failure despite the use of advanced therapeutic strategies for cancer treatment. As a result, many scientists are currently looking for newly repositioned drugs that can either inhibit cancer proliferation or promote cancer cell apoptosis. Methods: This study examined the effectiveness of pioglitazone (Pio) against mice bearing Ehrlich solid carcinoma in terms of its ability to inhibit cell proliferation and angiogenesis. Six groups were created using sixty male mice after the Ehrlich inoculation tumor growth was confirmed: control, Cis (5 ml/kg), Pio low dose (LD) (17.5 mg/kg), Pio high dose (HD) (30 mg/kg), Cis+Pio LD, and Cis+Pio HD. Different parameters, including behavioral, biochemical such as malondialdehyde (MDA), reduced glutathione, superoxide dismutase (SOD), tumor growth factors, and apoptotic TUNEL assay, were evaluated after three weeks in addition to Immunohistochemical analysis was done on the proliferating cell nuclear antigen (PCNA), hypoxia-inducible factor 1-alpha (HIF-1), PPAR, and cyclin D1. Results: Mice treated with Cis+Pio HD showed higher levels of SOD, GSH, p-ERK1/2 and p38-MAPK, as well as lower levels of MDA and tumor growth factor beside the higher apoptotic activity. Furthermore, Cis+Pio HD reduced the expression of PCNA and HIF-1 and increased the expression of PPARγ, which improved the histopathological changes. Conclusion: Pio possesses ESC-specific anticancer abilities. However, more research is needed before it can be used as an adjuvant agent to boost the therapeutic efficacy of chemotherapy in the treatment of many types of cancer.
Keywords | Pioglitazone; Cisplatin; Ehrlich solid carcinoma; Oxidative stress; VEGF; PPARγ; anticancer agents; tumorigenesis; biochemical indices
To share on other social networks, click on any share button. What are these?
