Radix Actinidiae chinensis induces the autophagy and apoptosis in renal cell carcinoma cells.

Renal cell carcinoma (RCC) is a malignant tumor. Radix Actinidiae chinensis (RAC) is the root of Actinidia arguta (Sieb. et Zucc) Planch. ex Miq. In clinical research, RAC was confirmed to have a certain anti-tumor effect, including liver cancer and cholangiocarcinoma. This study investigated the anticancer effect and mechanism of RAC in RCC cells. The 786-O and A498 cells were intervened with varying concentrations of RAC (0-100 mg/mL) to detect the half maximal inhibitory concentration (IC50) of RAC. The cells were then co-cultured with 0-50 mg/mL RAC for 0-72 h to assess the effect of RAC on cell viability using the cell counting kit-8. The effects on cell proliferation, cell cycle or apoptosis, migration or invasion, and autophagy were detected using cloning, flow cytometry, Transwell, AOPI assay and Western blot. The number of autophagolysosomes was quantified using a transmission electron microscope. PI3K/AKT/mTOR pathway-related proteins were detected by Western blot. Additionally, an autophagy inhibitor 3-MA was used to explore the underlying mechanism of RAC. IC50 values of RAC in 786-O and A498 were 14.76 mg/mL and 13.09 mg/mL, respectively. RAC demonstrated the ability to reduce the cell malignant phenotype of RCC cells, blocked the S phase of cells, promoted apoptosis and autophagy in cells. Furthermore, RAC was observed to increase autophagy-related proteins LC3II/I and Beclin-1, while decreasing the level of P62. The expression of apoptosis-related proteins was increased, while the ratios of p-PI3K/PI3K, p-AKT/AKT, p-mTOR/mTOR, p-P38/P38 and p-ERK/ERK were reduced by RAC. However, the addition of 3-MA reduced the apoptosis and autophagy- promotion effects of RAC on RCC cells. RAC induced the apoptosis and autophagy, to inhibit the progression of RCC cells. This study may provide a theoretical and experimental basis for clinical anti-cancer application of RAC for RCC.

Liu B ，Yan Y ，Zhang L 《-》

Radix Actinidia chinensis Suppresses Renal Cell Carcinoma Progression: Network Pharmacology Prediction and In Vivo Experimental Validation.

Renal cell carcinoma (RCC) is a frequent disease with limited curative methods. This study is aimed at investigating the role and mechanism of Radix Actinidia chinensis (RAC) on RCC. The ingredients, target, and crucial pathways of RAC in RCC therapy were analyzed by network pharmacology. Then, an RCC animal model was established by subcutaneously injecting A498 cell suspension to BALB/c nude mice. After 1 week, the mice in the RAC-L/M/H groups were administered with RAC at 5, 10, and 20 mg/kg/d, respectively. The histopathology of the tumor was evaluated. The contents of tumor inflammatory cytokines and serum oxidative stress factors were detected by ELISA. The apoptosis of tumor tissues was assessed by TUNEL staining. The expressions of apoptosis-, proliferate-, autophagy-, and MAPK-related proteins were measured. There were 13 active ingredients, and 20 RCC-relevant targets were selected from RAC; KEGG pathway indicated that these targets were enriched in the PI3K/AKT/mTOR and MAPK pathway. In in vivo experiments, RAC not only obviously damaged tumor cells and decreased the release of inflammatory cytokines and oxidative stress factors but also enhanced the apoptosis of the tumor cell in RCC mice. Besides, the expressions of apoptosis-, proliferate-, autophagy-, PI3K/AKT/mTOR path-, and MAPK path-related proteins were all affected by RAC. RAC attenuated RCC by regulating inflammation response, oxidative stress, apoptosis, proliferation, and autophagy, and its effects were partly linked to the PI3K/AKT/mTOR and MAPK pathway, which indicated that RAC may be a candidate drug for RCC.

Liu B ，Zhang L 《-》

β-Elemene induces apoptosis in human renal-cell carcinoma 786-0 cells through inhibition of MAPK/ERK and PI3K/Akt/ mTOR signalling pathways.

Zhan YH ，Liu J ，Qu XJ ，Hou KZ ，Wang KF ，Liu YP ，Wu B ... -  《-》

[Effect of licochalcone A on autophagy in renal cell carcinoma via PI3K/Akt/mTOR signaling pathway].

To investigate the effect of licochalcone (LCA) on autophagy in renal cell carcinoma (RCC), and further determine whether the mechanism is correlated with the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of mTOR pathway, RCC 786-O and 769-P were used as study subjects. MTT assay was used to examine cell proliferation. The abilities of migration and invasion were detected by Transwell. The autophagy was observed under the fluorescence microscope through acridine orange staining. Green fluorescence spots were observed in Ad-GFP-LC3 transfection experiment. The protein expression was detected by Western blot. MTT assay results showed a dose and time-dependent cytotoxicity in the two cell lines treated with LCA. LCA inhibited migration and invasion in 786-O and 769-P cells. LCA increased the expression levels of LC3-Ⅱ, beclin 1, Atg5, and down-regulated the expression of p62. In addition, LCA inhibited the PI3K/Akt/mTOR pathway. Furthermore, the inhibition of PI3K/Akt by LY294002 or that of mTOR by rapamycin augmented LCA-induced autophagy. The findings demonstrated that LCA inhibited the proliferation, migration, invasion, and induced autophagy by inactivating PI3K/Akt/mTOR signaling pathway in 786-O and 769-P cells.

Xin H ，Xu W 《-》

The pro-apoptosis effect of sinomenine in renal carcinoma via inducing autophagy through inactivating PI3K/AKT/mTOR pathway.

Renal cell carcinoma (RCC) is a heterogeneous histological disease and the most common kidney cancer. The mortality rate of RCC remains high despite the improved treatment. Sinomenine is an isoquinoline extracted from Chinese medicinal plant Sinomenium acutum, famous for its ability to suppress several cancer cell types. Our research aimed to explore the anti-cancer potential of sinomenine in RCC. Results showed that sinomenine reduced the viability by reducing sphere-forming ability and enhancing pro-apoptosis effect in ACHN cells in a dose dependent manner. The expression levels of proliferation/apoptosis markers further validated the result. In addition, sinomenine significantly regulated the level of autophagy-related proteins with decreased expression of p62, and increased Beclin1 and LC3 II/LC3 I. Furthermore, phosphatidylinositol-3 kinase (PI3K)/AKT/mechanistic target of rapamycin (mTOR), the negatively regulated cell autophagy signaling pathway, was inhibited by sinomenine with decreased membrane translocation of AKT in ACHN cell lines. All in all, our study demonstrated that sinomenine promoted apoptosis in RCC via enhancing autophagy through PI3K/AKT/mTOR pathway.

Deng F ，Ma YX ，Liang L ，Zhang P ，Feng J ... -  《-》