Poricoic acid A induces apoptosis and autophagy in ovarian cancer via modulating the mTOR/p70s6k signaling axis.

Rui Ma,Jin Xu,Xueqi Liang,Zhenhua Zhang,Qiang Zhao

doi:10.1590/1414-431x2021e11183

Abstract

Due to the high mortality and rapid disease progression, ovarian cancer remains one of the most common malignancies threatening the health of women. The present study was conducted to explore the anticancer effects and the underlying mechanisms of poricoic acid A (PAA), the main components of Poria cocos, on ovarian cancer. We investigated the anticancer effects of different concentrations of PAA in the SKOV3 cell line. Cell viability and proliferation were examined by CCK-8 assay. Cellular migration and invasion were assessed by the scratch and Transwell migration assays, respectively. The effect of PPA on cell apoptosis was measured by flow cytometry and caspase-3/8/9 colorimetric assay. Western blot was performed to detect protein level changes related to apoptosis and mTOR signaling pathways. The in vivo anticancer effect of PAA was evaluated using xenograft tumorigenesis model in nude mice. Our results showed that PAA suppressed SKOV3 cellular viability, migration, and invasion in a dosage-dependent manner. Flow cytometry results demonstrated PAA treatment could induce SKOV3 cell apoptosis. In addition, increased ratio of LC3-II/LC3-I (a marker for autophagosome formation) was observed after PAA treatment, as well as inhibition of m-TOR and p70s6k phosphorylation. In nude mice, PAA treatment reduced the xenograft tumor weight by 70% (P<0.05). In conclusion, our data suggested that PAA induced apoptosis and autophagy in ovarian cancer via modulating the mTOR/p70s6k signaling axis.

Highlights

Ovarian cancer is one of the most common lifethreating cancers in women
After 24 h treatment, Cell counting kit-8 (CCK-8) assay showed that poricoic acid A (PAA) treatment significantly decreased cell viability in a dosage-dependent manner, with a stronger effect at higher concentrations (Figure 1A)
We examined the effect of PAA on migration of SKOV3 cells using the cell scratch assay

Summary

Introduction

Ovarian cancer is one of the most common lifethreating cancers in women. Almost 300,000 women are diagnosed with ovarian cancer every year, which leads to roughly 180,000 deaths [1]. The prevalence of ovarian cancer increases with aging. The estimated incidence is 6.6% (per 100,000 women) below the age of 40 and the incidence rises to 48.6% (per 100,000 women) above the age of 65 [2,3]. Other risk factors include hereditary mutations, pregnancy history, fertility or infertility drug usage, tubal ligation history, diabetes mellitus, and body mass index [4]. The pathology of ovarian carcinogenesis remains unclear. Current theory postulates that recurrent ovulation would cause cyclical injuries and the insufficient repair of the epithelium cells may contribute to ovarian tumorigenesis

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Results

Conclusion