Saudi Journal of Pathology and Microbiology (SJPM)
Volume-5 | Issue-12 | 477-485
Original Research Article
HIF-1α Inhibits Caspase 3 Mediated Apoptosis and Promotes Tumor Growth of Prostatic Carcinoma through Up Regulation of Cyclophilin A.
Mariana F Gayyed, Medhat M. Soliman, Ahmed Zaki Mohamed Anwer, Ehab Rifat Tawfiek, Nehad M. Reda Abdel-Maqsoud
Published : Dec. 10, 2020
Abstract
Background: The management of prostate cancer may be difficult due to apoptosis resistance. HIF-1α (Hypoxia inducible factor 1α) and CypA (cyclophilin A) over expression promotes this resistance. Caspase 3 is a central executioner of the apoptosis pathway. Changed expression may correspond to tumor cell challenge. Aim: Evaluation of HIF-1α, CypA and Caspase 3 expressions in BPH (benign prostatic hyperplasia), PIN (prostatic intra-epithelial neoplasia) and PCa (prostatic carcinoma). Methods: One hundred four patients with histologically diagnosed prostatic carcinoma, 20 cases with BPH and 24 cases with PIN were investigated. Immunohistochemical assessment was executed to evaluate HIF-1α, CypA and Caspase 3 expressions. Results: In BPH cases, HIF-1α, CypA and Caspase 3 were expressed in 20%, 30% and 60% respectively. In PIN cases, HIF-1α, CypA and Caspase 3 were expressed in 33.3%, 41.7% and 41.7%, respectively while in PCa cases, HIF-1α, CypA and Caspase 3 were expressed in 57.7%, 69.2% and 25% respectively. Increasing stage of prostatic cancer showed a significant increased HIF-1α and CypA immuno-expression with lost caspase 3 immuno-expressions. Conclusions: Distorted HIF-1α, CypA and Caspase 3 expressions may act as a further mechanism of apoptotic resistance in prostatic carcinoma treatment.