Kangfuxin promotes apoptosis of gastric cancer cells through activating ER-stress and autophagy

Chen, Pianpian; Ma, Xiaolong; Lin, Qian; Xu, He‐Lin; Shi, Hongxue; Zhang, Hongyu; Xiao, Jian; Geng, Funeng; Zhao, Ying‐Zheng

doi:10.3892/mmr.2017.7716

Cited by 19 publications

(11 citation statements)

References 36 publications

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“…Although our group has previously confirmed the gastroprotective effects of KFX in ethanol-induced gastric ulcer and gastric cancer (Chen et al. 2017; Shen et al. 2017), little is known about its potential therapeutic effects on stress-induced gastric ulcer.…”

Section: Discussionmentioning

confidence: 87%

Gastroprotective effects of Kangfuxin against water-immersion and restraint stress-induced gastric ulcer in rats: roles of antioxidation, anti-inflammation, and pro-survival

Sun

et al. 2019

Pharmaceutical Biology

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2019) Gastroprotective effects of Kangfuxin against water-immersion and restraint stress-induced gastric ulcer in rats: roles of antioxidation, anti-inflammation, and prosurvival, Pharmaceutical Biology, 57:1, 770-777, ABSTRACTContext: Kangfuxin (KFX) is widely used for the treatment of gastric and duodenal ulcer; however, more research is needed to determine the protective mechanisms of KFX in ameliorating gastric ulcer. Objective: To investigate the efficacy and potential mechanism of Kangfuxin liquid (KFX) in water-immersion and restraint stress (WIRS)-induced gastric ulcer. Materials and methods: Seventy rats were randomly divided into seven groups (n ¼ 10) as follows: the control group (normal saline, i.g.), the model group (normal saline, i.g.), the KFX groups (2.5, 5 and 10 mL/kg, i.g.), the omeprazole group (20 mg/kg, i.p.) and Sanjiuweitai Granules group (1850 mg/kg, i.g.).The WIRS model was applied to induce stress ulcers after 7 days of drug administration. Afterwards, rats were sacrificed at 10 h induced by WIRS. Results: Pre-treatment with KFX (5,10 mL/kg) could effectively reduce the area of gastric ulcers and improve the pathological changes of ulcerated tissue. Moreover, KFX (5,10 mL/kg) increased the prostaglandin E2 (52%) and cyclooxygenase-1 (30%) levels, and improved malondialdehyde (54%), superoxide dismutase (58%), catalase (39%), and nitric oxide (11%) and TNF-a (9%), IL-6 (11%), MMP-9 (54%) and MMP-2 (53%) of ulcer tissue. Furthermore, pre-treatment with KFX dramatically increased IGF-1, PTEN, and Akt protein expression. Conclusions: Our results suggest that KFX has protective effects on WIRS-induced gastric ulcer via inflammatory reactions, oxidative stress inhibition, and pro-survival action, which were the results of activating the IGF-1/PTEN/Akt signalling pathway. Our results provide evidence of KFX for treating gastric ulcer. ARTICLE HISTORY

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Section: Discussionmentioning

confidence: 87%

Gastroprotective effects of Kangfuxin against water-immersion and restraint stress-induced gastric ulcer in rats: roles of antioxidation, anti-inflammation, and pro-survival

Sun

et al. 2019

Pharmaceutical Biology

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“…31 The study of Ogata M et al indicated that there was a close relation between targeting the autophagy mechanisms and ER stress pathway. 32 ER stress and autophagy seems to be critical for oncogenesis and cell homeostasis. Melatonin, a naturally occurring compound with clear potent inhibitory effects on cancer cells is one of the main candidates, which can be recruited herein.…”

Section: Discussionmentioning

confidence: 99%

<p>The Therapeutic Effect of Melatonin on GC by Inducing Cell Apoptosis and Autophagy Induced by Endoplasmic Reticulum Stress</p>

Zheng¹,

Tu²,

Wang³

et al. 2019

OTT

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Background: Gastric cancer (GC) is the main malignancy affecting a large population worldwide. Lack of effective enough treatment is one of the leading factors contributing to the high mortality rate. Melatonin, a naturally occurring compound, has been proven to exert cytotoxic and antiproliferative effects on human gastric cancers. Nevertheless, the mechanisms of anti-gastric cancer of melatonin remain elucidated. It is believed that endoplasmic reticulum (ER) stress and its resultant unfolded protein response (UPR) are connected to the survival, progression, and chemoresistance of various tumor cells via multiple cellular procedures, such as autophagy. In this study, the effects of melatonin on human gastric cancer cell lines AGS and SGC-7901 was assessed to reveal the interaction between melatonin, endoplasmic reticulum stress, and autophagy in gastric cancer. Methods: CCK-8, the wound healing analysis, colony formation assay, immunofluorescence analysis, Western blotting, flow cytometry, and animal models were used in the current study. Results: The data demonstrated that melatonin could inhibit GC growth, proliferation, and invasion both in vivo and in vitro. Apoptosis and autophagy induced in a concentrationdependent manner is response to melatonin-induced ER stress. Melatonin induced the expression of apoptotic and autophagy-related proteins, which was markedly attenuated by the ER stress inhibitor 4-PBA and autophagy inhibitor 3-MA. In addition, we used the specific IRE1 inhibitor STF 083010, finding that inhibiting IRE1 could considerably relieve ER stress-induced autophagy activity, as revealed by the reduction of LC3-II and Beclin-1. Conclusion: This study confirmed that melatonin-induced inhibition of GC cell proliferation is mediated by the activation of the IRE/JNK/Beclin1 signaling.

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“…Therefore, investigation into more effective therapeutic interventions for gastric cancer is important. Over the last 50 years, emerging evidence has suggested that a number of natural extracts from plants and animals exhibit beneficial effects in the prevention of cancer ( 16 , 38 , 39 ). The present study demonstrated that KFX, an aqueous extract from P. americana , exhibited potential anticancer effects in a gastric cancer cell line through inhibiting cell proliferation and inducing apoptosis; potentially via the ERK signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

“…Several novel drugs, including Kangfuxin (KFX) oral liquid, Xinmailong injection and cockroach oil have been developed using P. americana as the raw material, with recognized pharmacological activity and clinical efficacy ( 11 – 14 ). A previous study revealed that P. americana extract exhibited significant anticancer effects on the BEL-7402/5-FU Cell line and SGC-7901 cell line ( 15 , 16 ). However, the exact apoptotic effect of KFX remains unclear.…”

Section: Introductionmentioning

confidence: 98%

Pro‑apoptotic effects of Kangfuxin on human stomach cancer cells and its underlying mechanism

Ma¹,

Sun

et al. 2018

Oncol Lett

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Kangfuxin (KFX) is an oral liquid derived from Periplaneta americana, with complex components. KFX has been demonstrated to exhibit anticancer activity in a variety of different types of tumor, including gastric cancer; however, its underlying molecular mechanism remains unclear. The present study was designed to investigate the pro-apoptotic effects of KFX on SGC-7901 cells, in order to provide a theoretical basis for clinical application. In order to clarify the pro-apoptotic effects of KFX on SGC-7901 cells, MTT analysis was conducted. To evaluate the anticancer effect of KFX, peroxisome proliferator-activated receptor (PPAR)-γ was analyzed by reverse transcription-polymerase chain reaction. Western blot analysis was used to determine the effects of KFX on the expression of cleaved caspase-3, phosphorylated extracellular signal-regulated kinase (p-ERK), ERK, tumor protein p53 (p53), B-cell lymphoma 2 (Bcl-2), Bcl-2 associated X, interleukin (IL)-6 and IL-1β. In addition, terminal deoxynucleotidyl-transferase-mediated dUTP nick-end labeling (TUNEL) analysis was used to detect apoptosis in SGC-7901 cells. It was revealed that PPAR-γ was increased in SGC-7901 cells following treatment with KFX, shown by an increase in mRNA expression. Furthermore, western blot analysis identified that KFX treatment groups exhibited markedly inhibited levels of Bcl-2, IL-6, IL-1β and p-ERK, and induced p53 protein expression. Additionally, TUNEL and MTT assays demonstrated that treatment with KFX may induce SGC-7901 cell apoptosis and inhibit proliferation. In conclusion, to the best of our knowledge, the results of the present study demonstrated for the first time that KFX may induce SGC-7901 cell apoptosis and inhibit its proliferation, and this may be primarily attributed to its role in mitogen-activated protein kinase/extracellular-signal-regulated kinase kinase/ERK signaling pathway inhibition.

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Kangfuxin promotes apoptosis of gastric cancer cells through activating ER-stress and autophagy

Cited by 19 publications

References 36 publications

Gastroprotective effects of Kangfuxin against water-immersion and restraint stress-induced gastric ulcer in rats: roles of antioxidation, anti-inflammation, and pro-survival

Gastroprotective effects of Kangfuxin against water-immersion and restraint stress-induced gastric ulcer in rats: roles of antioxidation, anti-inflammation, and pro-survival

<p>The Therapeutic Effect of Melatonin on GC by Inducing Cell Apoptosis and Autophagy Induced by Endoplasmic Reticulum Stress</p>

Pro‑apoptotic effects of Kangfuxin on human stomach cancer cells and its underlying mechanism

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