Curcumin Nanoparticle Enhances the Anticancer Effect of Cisplatin by Inhibiting PI3K/AKT and JAK/STAT3 Pathway in Rat Ovarian Carcinoma Induced by DMBA.

Ni Made Dwi Sandhiutami,Melva Louisa,Puspita Eka Wuyung,Wawaimuli Arozal,Deni Rahmat

doi:10.3389/fphar.2020.603235

Ni Made Dwi Sandhiutami, Melva Louisa + Show 3 more

Open Access

https://doi.org/10.3389/fphar.2020.603235

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Abstract

Cisplatin has been used for decades for the treatment of ovarian cancer. However, despite its potent anticancer effect, cisplatin’s efficacy as a single agent was inadequate in patients with advanced stage. Curcumin has been shown to sensitize cisplatin activity in several cancer models. However, the low bioavailability of curcumin has limited its anticancer potential. Hence, nano-formulation of curcumin was developed to increase its therapeutic efficacy in ovarian cancer. The objective of this study was to investigate the mechanism of curcumin nanoparticles given in combination with cisplatin in rat ovarian carcinoma induced by dimethylbenz(a)anthracene (DMBA). The administration of cisplatin and nanocurcumin resulted in a significant reduction in ovarian tumor volume and weight. Furthermore, there were reduction in expressions of Ki67, TGF-β, PI3K, and Akt phosphorylation. Co-treatment of cisplatin and nanocurcumin also reduced JAK expression, STAT3 phosphorylation, and reduced IL-6 concentrations. Altogether, nanocurcumin, given as a co-treatment with cisplatin has therapeutic potential in ovarian cancer models by inhibiting proliferation through downregulation of PI3K/Akt and JAK/STAT3 signaling pathways.

Highlights

Ovarian cancer is the leading cause of mortality and is currently one of the five most common women cancers globally
We demonstrated that cisplatin plus nanocurcumin has a synergistic effect by generating antiproliferation and apoptosis in ovarian cancer animal models by downregulation of PI3K/ AKT and JAK/STAT3 signaling pathway
Our study demonstrates that nanocurcumin potentiates the anticancer effect of cisplatin by reducing tumor volume and weight

Summary

Introduction

Ovarian cancer is the leading cause of mortality and is currently one of the five most common women cancers globally. It is estimated that by the year of 2040, cancer mortality rates will increase significantly (Bray et al, 2018). In the case of ovarian cancer, the high cancer mortality rate is caused due to asymptomatic symptoms, delayed onset of symptoms, late diagnosis, and lack of proper screening. All of these factors result in tendency for ovarian cancer to be diagnosed at an advanced stage with four out of five ovarian cancer patients are diagnosed at an advanced stage. The most common chemotherapy used is platinum (cisplatin or carboplatin)

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