Ginkgolic acid induces apoptosis and autophagy of endometrial carcinoma cells via inhibiting PI3K/Akt/mTOR pathway in vivo and in vitro

Abstract

Endometrial cancer (EC) is the fourth most common malignancy in women in developed countries. The prognosis of EC is extremely poor, and it is an important factor that contributes to the death of patients. Therefore, studying EC pathogenesis and therapeutic targets, and exploring effective drugs are the primary tasks to improve the prognosis of EC. In the present study, we aimed to explore the function of ginkgolic acid (GA) in EC cell apoptosis and autophagy through PI3K/Akt/mTOR signal pathway in vitro and in vivo. Firstly, MTT assay and clone formation assay were employed to analyze the Ishikawa and HEC-1-B cell viabilities and proliferation after treatment with GA. The results showed that GA inhibited endometrial cancer cell survival. Flow cytometry assay and western blot assay were applied to examine the apoptosis and apoptosis related protein Bcl-2, Bax, Cleaved caspase-3 expression levels of Ishikawa and HEC-1-B cells after treatment with GA. Next, we applied western blot assay to analyze the autophagy associated proteins LC3I, LC3II, p62 and Beclin-1 in GA treated Ishikawa and HEC-1-B cells. We found that GA promoted apoptosis and induced autophagy of endometrial cancer cells. Meanwhile, western blot assay was also used to determine the expression levels of the PI3K/Akt/mTOR signal pathway related protein and the results revealed that GA inhibited the activity of PI3K/Akt/mTOR pathway. Finally, we found that GA inhibited tumor growth in vivo through immunohistochemistry assay. In conclusion, GA induces apoptosis and autophagy of EC cells via inhibiting PI3K/Akt/mTOR pathway in vivo and vitro.

Smp24, a Scorpion-Venom Peptide, Exhibits Potent Antitumor Effects against Hepatoma HepG2 Cells via Multi-Mechanisms In Vivo and In Vitro

“…Furthermore, the PI3K/Akt/mTOR pathways are regarded as promising targets for cancer therapy due to their important role in the process of cell proliferation, growth, survival, and mobility [ 46 ]. Consequently, multiple candidate anticancer agents suppress tumor growth by inhibiting PI3K/Akt/mTOR pathways and then inducing autophagy, as well as apoptosis of cancer cells [ 47 , 48 ]. In line with these, Smp24 suppressed the phosphorylation of PI3K/Akt/mTOR and increased the autophagic flux of LC3A/B-II/I, as well as the degradation of p62 ( Figure 8 A,B).…”

Advances in research on autophagy mechanisms in resistance to endometrial cancer treatment

“…A multitude of research has shown that blocking the PI3K/AKT/mTOR pathway may lead to heightened cellular autophagy processes. Within the EC cell lines Ishikawa and HEC1-B, escalating levels of ginkgolic acid progressively suppressed the PI3K/AKT/mTOR pathway, boosting autophagy in cancerous cells, thus curtailing cell growth and triggering apoptosis ( 75 ). Inhibiting the PI3K/AKT/mTOR pathway in EC cell lines HEC-1A and Ishikawa led to increased autophagy activity and reduced cancer cell proliferation, migration, and invasion, achieved by inhibiting FAM83B, a Family 83 member with similar sequences.…”

TP53BP2: Roles in suppressing tumorigenesis and therapeutic opportunities

“… 82 The PI3K/AKT pathway is a key regulator of survival during cell stress, and abnormal activation of this pathway is often observed in tumors. 13 , 83 , 84 , 85 A recent study showed that inhibiting TP53BP2 expression promotes the growth and migration of triple negative breast cancer (TNBC) cells through this pathway. 13 PI3KR1 (P85 α) negatively regulates the PI3K pathway.…”