Increased levels of COX-2 mRNA, protein, and prostaglandin E(2) synthesis were detected in HPV16 E6- and E7-expressing cervical cancer cells (CaSki and SiHa) compared with an uninfected cervical cancer cell line (C33A).
Thus reduced miR-101 expression could participate in the development of cervical cancer at least partly through loss of inhibition of target gene COX-2, which probably occurs in a relative late phase of carcinogenesis.
The CaSki + vehicle group also showed significantly increased COX-2, EGFR, p-ERK1&2, and p-AKT; however they were attenuated by all treatments with THC.
This meta-analysis indicated that COX-2 overexpression might be an unfavorable prognostic and a chemoradiation resistance predictive factor for cervical cancer; it could potentially help to stratify patients further in clinical treatment.
These results confirm that COX-2, EP2, and EP4 expression and PGE(2) synthesis are up-regulated in cervical cancer tissue and suggest that PGE(2) may regulate neoplastic cell function in cervical carcinoma in an autocrine/paracrine manner via the EP2/EP4 receptors.
The assessment of COX-2 status could provide additional information to identify patients with cervical cancer with a poor chance of response to neoadjuvant treatment and unfavorable prognosis.
These results indicate that COX2 is a novel resistance factor of DCA, and combination of celecoxib with DCA may be beneficial to the treatment of cervical cancer.
The finding that TIMP-2 and COX-2 expression in cervical cancer may be affected by the stage of the menstrual cycle supports the hypothesis that ovarian hormones may affect the expression of genes involved in metastasis.
Further studies evaluating the role of COX-2 gene polymorphisms in ethnically diverse populations and a larger cohort may help in understanding the etiopathogenesis of cervical cancer in women worldwide.