Curcumol Targeting PAX8 Inhibits Ovarian Cancer Cell Migration and Invasion and Increases Chemotherapy Sensitivity of Niraparib

Abstract

Objective. To investigate the effects of Curcumol on invasion, migration and epithelial-mesenchymal transformation of IGROV-1 and OVCAR-3 cells in ovarian cancer and its potential mechanism. Meanwhile, the effect of Curcumol on the antitumor activity of Niraparib was analyzed. Methods. Cell Counting Kit 8 (CCK-8) was used to detect the effects of Curcumol on the activity of IGROV-1 and OVCAR 3 cells. In vitro invasion assay (Transwell) was used to test the invasiveness of cells. Cell migration was detected by scratch assay. The inhibitory effect of Curcumol on PAX8 was detected by QRT-PCR. To evaluate the antitumor effect of Curcumol in subcutaneous tumor-bearing animal model. Results. Knockdown of PAX8 could inhibit the proliferation, invasion and migration of ovarian cancer cells. After Curcumol treated IGROV-1 and OVCAR-3 cells, the cell proliferation ability was decreased, the number of invasive cells was significantly reduced, and the scratch closure rate was significantly reduced, in a dose-dependent manner. Mechanism studies showed that Curcumol increased the antitumor activity of Niraparib by inhibiting PAX8. Conclusion. Curcumol can inhibit the invasion, migration and epithelial-mesenchymal transformation of IGROV-1 and OVCAR-3 cells in ovarian cancer, and its mechanism is related to the targeted inhibition of PAX8. Curcumol also increased the sensitivity of Niraparib chemotherapy by inhibiting PAX8.

Micellar Curcumol for Maintenance Therapy of Ovarian Cancer by activating the FOXO3a

“…Clinically, curcumol has been regarded as a sensitizer or an adjuvant chemotherapy drug for OC [10]. Although curcumol has been proven to be effective against gynecological tumors [10,14], its low bioavailability, rapid metabolism, and poor enrichment in tumor regions restrain its broad use for OC treatment [15]. Polymeric micelles (PMs) can load hydrophobic drugs in the micellar hydrophobic core, and the drug can be protected by the outer hydrophilic corona, which can further prevent micelles from being eliminated by the mononuclear phagocytic system (MPS) in physical circulation, thereby prolonging the in vivo circulation time [16].…”

Pharmacokinetics, tissue distribution, and plasma protein binding rate of curcumol in rats using liquid chromatography tandem mass spectrometry

“…Curcumol is one of the primary active ingredients of traditional Chinese medicine Curcumae Rhizom a, which has been used to treat cancer in clinical combination therapies ( Aghaabbasi et al, 2020 ). Curcumol exhibits tumor-suppressive activity in various cancer types, such as hepatocellular carcinoma, nasopharyngeal carcinoma, lung adenocarcinoma, pancreatic, ovary, and breast cancer ( Lu et al, 2012 ; Zuo et al, 2020 ; Tian et al, 2021 ; Fang et al, 2022 ; Liu, 2022 ). Curcumol also increased the sensitivity of cancer cells to cytotoxic antitumor drugs in the gastric and colon ( Huang et al, 2020 ; Gao et al, 2021 ).…”