Celastrus Orbiculatus Extracts Inhibit the Metastasis through Attenuating PI3K/Akt/mTOR Signaling Pathway in Human Gastric Cancer

Qian, Yayun; Yan, Yan; Lü, Hongmei; Zhou, Tingting; Lv, Mengying; Fang, Chuanci; Hou, Jingjing; Li, Wenyuan; Chen, Xiwen; Sun, Hui; Li, Yajuan; Wang, Zheng; Zhao, Nan; Gu, Yajuan; Ding, Yun; Liu, Yanqing

doi:10.2174/1871520619666190731162722

Cited by 14 publications

(5 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As shown in Figure 3A, uorescence analysis showed that BBD treatment severely disrupted cell morphology. Western blot analysis demonstrated that BBD treatment highly induced autophagy-related signals of LC3 I/II and Beclin 1, but suppressed p62, leading to autophagy in SGC7901/DDP cells ( Figure 3E and 3F) Activation of the PI3K/AKT/mTOR signaling pathway has been shown to have carcinogenic effects in gastric cancer, and its regulatory pathways are closely related to genetic variation, cell proliferation, migration, invasion, cell cycle, apoptosis, autophagy, angiogenesis, multi-drug resistance and cell viability [21,[39][40][41][42][43][44][45][46]. Guo et al found that Ubenimex inhibited the phosphorylation and activation of the PI3K/AKT/mTOR pathway and down-regulated membrane transporter (such as p-gp and MRP1) expression, resulting in the intracellular accumulation of 5-uorouracil and oxaliplatin [47].…”

Section: Discussionmentioning

confidence: 99%

Babao dan promotes apoptosis of cisplatin (DDP)-resistant gastric cancer cell line SGC-7901/DDP by inducing autophagy through PI3K/AKT/mTOR pathway modulation

Zhao¹,

W²,

Peng³

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Multidrug resistance (MDR) is a critical reason of cancer chemotherapy failure. Babao dan (BBD) is a classical and famous traditional Chinese patent medicine, which has been reported to has anti-gastric cancer activity. However, the roles and molecular mechanisms of the reversal of MDR of gastric cancer by BBD have not been well described until now. Methods: SGC-7901 and SGC-7901/DDP cells were used in this study, and drug resistance and evaluation of the reversal effect of BBD was determined using MTT assays in SGC7901/DDP cells. Doxorubicin (DOX) and Rhodamin123 (Rho123) staining was performed to assess BBD effects on drug accumulation and efflux of drug-resistant gastric cancer cells. Cell apoptosis was directly assessed using DAPI staining. Apoptotic and dead cells were detected by flow cytometry after staining with Annexin V-FITC and propidium iodide (PI). Cyto-ID assays were performed to examine cellular autophagy. Changes in cell protein expression of ABCB1, ABCC1, ABCG2, Bax, Bcl-2, caspase-3, cleaved-caspase-3, LC3, p62, Beclin1 and the PI3K/AKT/mTOR pathway were detected by Western blot. Inhibition of autophagy with 3-MA, chloroquine (CQ) and PI3K antagonist (LY294002) or agonist (740Y-P) , uncovered a role for the potentially downregulated signaling pathway, PI3K/AKT/mTOR.Results: The SGC7901/DDP cell line exhibited multi-drug resistance to DDP, DOX and 5-fluorouracil (5-FU) and the drug resistant index (RI) of DDP, DOX and 5-FU were 1.86, 1.50 and 47.70, respectively. BBD reversed the MDR of SGC7901/DDP cells by increasingDOX accumulation, reducing Rh123 efflux and down-regulating the expression of ABCB1, ABCC1, ABCG2. Furthermore, BBD induced apoptosis in SGC7901/DDP cells through regulating caspase-3, cleaved-caspase-3, Bax and Bcl-2. Moreover, BBD induced autophagy in DDP-resistant gastric cancer cells via regulating p62, LC3 and Beclin1. Pathway analyses suggested BBD may inhibit PI3K/AKT/mTOR pathway activity and subsequent autophagy induction. Conclusions: BBD may reverse the MDR of gastric cancer cells, and promote autophagic death via inactivation of the PI3K/AKT/mTOR signaling pathway.

show abstract

Section: Discussionmentioning

confidence: 99%

Babao dan promotes apoptosis of cisplatin (DDP)-resistant gastric cancer cell line SGC-7901/DDP by inducing autophagy through PI3K/AKT/mTOR pathway modulation

Zhao¹,

W²,

Peng³

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Fortunately, multiple GC cell lines (MGC-802, BGC-823, AGC) have been applied in previous research to investigate the effect of COE treatment on the growth, invasion, and metastasis of GC. 63 - 65 Relevant results indicated that COE could effectively inhibit the growth, invasion, and metastasis of GC in different GC cell lines, which may be able to partially compensate the lack of study. At present, our research group is isolating and identifying CSC-like cells using the HGC-27 cell line to explore the effect of COE on the differentiation of GCSCs.…”

Section: Discussionmentioning

confidence: 99%

Celastrus orbiculatus Extract Reduces Stemness of Gastric Cancer Stem Cells by Targeting PDCD4 and EIF3H

Zhu

Chen

et al. 2021

Integr Cancer Ther

View full text Add to dashboard Cite

Background Celastrus orbiculatus ethyl acetate extract (COE) has shown a strong anti-gastric cancer effect, but the understanding of its mechanism is still lacking. The results of previous studies indicated that COE may be able to inhibit the stemness of gastric cancer stem cells (GCSCs) by regulating PDCD4 and EIF3H expression. Aims To explore if COE could inhibit the stemness of GCSCs by regulating PDCD4 and EIF3H expression in vitro and in vivo. Procedure The GCSCs model was established by stem cell-conditioned culture. Spheroid formation and flow cytometry assays were used to detect the effect of COE on the spheroid formation ability of GCSCs and the percentage of CD44+/CD24+ and ALDH+ cell subpopulations. Western blot analysis was applied to measure the expression of GCSCs biomarkers (Nanog, Oct-4, and SOX-2), PDCD4, and EIF3H in GCSCs treated with COE; and RT-PCR was performed to investigate the effect of COE on PDCD4 mRNA expression in GCSCs. An in vivo tumorigenicity experiment was also conducted to evaluate the effect of COE on tumor-initiating ability of GCSCs in vivo; and the expression of PDCD4 and EIF3H in xenograft tissues was examined by immunohistochemistry (IHC) staining. Results After culture in stem cell-conditioned medium, SGC7901 cells manifested significantly enhanced spheroid formation ability, upregulated Nanog, Oct-4, and SOX-2 expression and increased percentages of CD44+/CD24+ and ALDH+ cell subpopulations, indicating successful establishment of the GCSCs model. COE treatment significantly inhibited the spheroid formation ability of GCSCs and reduced the percentage of CD44+/CD24+ and ALDH+ cell subpopulations. The western blot analysis showed a significant decrease of Nanog, Oct-4, SOX-2, and EIF3H expression and an increase of PDCD4 expression in GCSCs after COE treatment in a concentration-dependent manner. COE treatment also significantly upregulated the mRNA expression of PDCD4 in GCSCs. In addition, COE displayed a strong inhibitory effect on the tumor-initiating ability of GCSCs in vivo and upregulated PDCD4 and downregulated EIF3H expression in xenograft tissues. Conclusion COE may be able to inhibit GC growth by suppressing the stemness of GCSCs via regulating PDCD4 and EIF3H expression.

show abstract

“…The PI3K/AKT signaling pathway has been identified to play an important role in the progression of various cancer types, including GC (27)(28)(29). Once the PI3K/AKT signaling pathway is activated, phosphorylation of AKT directly regulates the expression of a range of proteins involved in cell metabolism, proliferation, motility, invasion and migration.…”

Section: Discussionmentioning

confidence: 99%

Upregulation of circRNA_100395 sponges miR‑142‑3p to inhibit gastric cancer progression by targeting the PI3K/AKT axis

et al. 2021

View full text Add to dashboard Cite

Gastric cancer (GC) has a high morbidity and mortality, hence it is very important to elucidate the molecular pathogenesis mechanism of GC progression in order to find new treatment strategies. The present study aimed to explore the biological function of circular RNA_100395 (circRNA_100395) in GC. The expression level of circRNA_100395 in GC tissues, as well as normal epithelial cells and various gastric cancer cell lines, was detected using reverse transcription-quantitative PCR. Cell Counting Kit-8, EdU assay, flow cytometry and Transwell assays were performed to investigate cell proliferation, apoptosis, migration and invasion, respectively. A dual-luciferase reporter assay was performed to detect the correlation between circRNA_100395 and micro (mi)RNA-142-3p. Western blotting was performed to elucidate the potential regulatory mechanism. circRNA_100395 expression was found to be increased in GC tissues and cell lines. However, miR-142-3p expression was significantly reduced. Besides, low expression levels of circRNA_100395 were associated with poor tumor differentiation, advanced Tumor-Node-Metastasis stage, lymph node metastasis and shorter overall survival time. Moreover, overexpression of circRNA_100395 suppressed cell proliferation, increased the apoptosis rate and suppressed cell invasion and migration by inhibiting the PI3K/AKT signaling pathway. These findings also showed that miRNA-142-3p rescued the antitumor effects induced by circRNA_100395-overexpression. cirRNA_100395-overexpression had antitumor effects via regulating the miR-142-3p signaling pathway, which might be a promising treatment target for GC.

show abstract

Celastrus Orbiculatus Extracts Inhibit the Metastasis through Attenuating PI3K/Akt/mTOR Signaling Pathway in Human Gastric Cancer

Cited by 14 publications

References 23 publications

Babao dan promotes apoptosis of cisplatin (DDP)-resistant gastric cancer cell line SGC-7901/DDP by inducing autophagy through PI3K/AKT/mTOR pathway modulation

Babao dan promotes apoptosis of cisplatin (DDP)-resistant gastric cancer cell line SGC-7901/DDP by inducing autophagy through PI3K/AKT/mTOR pathway modulation

Celastrus orbiculatus Extract Reduces Stemness of Gastric Cancer Stem Cells by Targeting PDCD4 and EIF3H

Upregulation of circRNA_100395 sponges miR‑142‑3p to inhibit gastric cancer progression by targeting the PI3K/AKT axis

Contact Info

Product

Resources

About