Chinese herbal medicine Fuzheng Kang-Ai decoction sensitized the effect of gefitinib on inhibition of human lung cancer cells through inactivating PI3-K/Akt -mediated suppressing MUC1 expression

Li, Longmei; Wang, SuMei; Zheng, Fang; Wu, Wanyin; Hann, Swei Sunny

doi:10.1016/j.jep.2016.10.077

Cited by 16 publications

(13 citation statements)

References 52 publications

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“…Our previous studies have shown that FZKA decoction inhibited lung cancer cell growth through multiple mechanisms [ 11 , 12 ]. We then explored the potential mechanism by which FZKA affected apoptosis in NSCLC cells.…”

Section: Resultsmentioning

confidence: 99%

“…More importantly, the combination of FZKA decoction and gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), has a synergistic effect on NSCLC cells. The in vitro and in vivo studies have provided a potential novel mechanism by which the FZKA decoction enhances the growth inhibition of gefitinib in gefitinib-resistant NSCLC cells [ 12 ]. Herein, we provided more evidences to demonstrate the proapoptotic effects of FZKA in lung cancer cells.…”

Section: Introductionmentioning

confidence: 99%

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Decoction of Chinese Herbal Medicine Fuzheng Kang‐Ai Induces Lung Cancer Cell Apoptosis via STAT3/Bcl‐2/Caspase‐3 Pathway

Wang

Long

Xiao

et al. 2018

Evidence-Based Complementary and Alternative Medicine

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Decoction of Chinese herbal medicine (CHM) Fuzheng Kang-Ai (FZKA for short) has been applied as adjuvant treatment strategy in advanced lung cancer patients for decades. We previously showed that FZKA decoction inhibited proliferation of non-small cell lung cancer (NSCLC) cells through activation of AMP-activated protein kinase alpha (AMPKα) signaling pathway, followed by inducing insulin-like growth factor (IGF) binding protein 1 (IGFBP1) and forkhead homeobox type O3a (FOXO3a) proteins, and enhanced the inhibition effect of gefitinib in lung cancer cell growth via inactivating PI3-K/Akt-mediated suppressing of cell surface-associated mucin-1 (MUC1) expression. In this study, we investigated the molecular mechanism by which FZKA decoction affected cell apoptosis in lung cancer cells. Our results show that FZKA induced apoptosis in lung cancer cells. Mechanistically, FZKA activated the caspase-3, PARP, and caspase-9 activities. Both antiapoptotic and proapoptotic proteins from Bcl-2 family were deregulated by FZKA exposure in lung cancer cells. In addition, FZKA reduced protein expressions of signal transducer and activator of transcription 3 (STAT3) and Jun activation domain-binding protein 1 (Jab1), while it concomitantly increased p21 protein. Moreover, the inhibitor of caspase-3 resisted the effect of FZKA on induction of apoptosis. Finally, exogenous overexpression of STAT3 overcame FZKA-inhibited protein expressions of Bcl-2 and myeloid cell leukemia-1 (Mcl-1) as well as Bax and blocked FZKA-induced activities of caspase-3 and caspase-9. Our results show that FZKA decoction promotes lung cancer cell apoptosis through STAT3/Bcl-2/caspase-3 signaling pathways. This study unveils potential novel molecular mechanism by which FZKA controls growth of human lung cancer cells.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Decoction of Chinese Herbal Medicine Fuzheng Kang‐Ai Induces Lung Cancer Cell Apoptosis via STAT3/Bcl‐2/Caspase‐3 Pathway

Wang

Long

Xiao

et al. 2018

Evidence-Based Complementary and Alternative Medicine

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“…And FZKA could also enhance the disease control rate (DCR) as well as median survival time (MST) in patients with NSCLC [9,10]. Mechanistically, we previously found that FZKA decoction could inhibit the growth of lung cancer cells through AMPKα/IGFBP1/FOXO3a, and PI3-K/Akt/NF-κB pathways, demonstrating its definite effect in treating lung cancer [11,12]. The above study showed that FZKA could inhibit the cell growth of lung cancer.…”

Section: Introductionmentioning

confidence: 83%

Fuzheng Kang-Ai decoction enhances the effect of Gefitinib-induced cell apoptosis in lung cancer through mitochondrial pathway

Wang

Peng

et al. 2020

Cancer Cell Int

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Background: Our previous clinical study has shown that Chinese herbal medicine (CHM) Fuzheng Kang-Ai (FZKA) decoction is effective in treating advanced lung cancer patients through prolonging the drug resistance to Gefitinib (GFTN). Our basic study found that FZKA decoction could enhance the inhibition effect of GFTN in lung cancer by inactivating PI3K/Akt pathway. Moreover, our recent work showed that FZKA induced lung cancer cell apoptosis via STAT3/Bcl-2/Caspase-3 pathway. Thus in this study, we aim to elucidate how FZKA enhances the effect of GFTN in lung cancer from the perspective of cell apoptosis. Methods: Cell proliferation and colony formation assay were performed to detect the cell growth inhibition. Flow cytometry and TUNEL assay were carried out to test the cell apoptosis. Mitochondrial membrane potential (MMP) assay was done to measure the alteration of MMP. Caspase-3/-9 activity assay was used to test the activity of caspase-3/-9. Western blot and qRT-PCR were done to detect the expression of STAT3 and Bcl-2 family as well as Caspase-3/-9 and Cyt-C at protein and mRNA levels, respectively. Transient transfection was performed to silence STAT3 using siSTAT3. Animal model was done to validate the molecular mechanisms in vivo and immunohistochemistry was done to detect the expression of Bax and Caspase-3. Results: Firstly, our results showed that FZKA enhanced the inhibition effect of GFTN in lung cancer both in vitro and in vivo. Secondly, cell apoptosis was enhanced when treating lung cancer cells with both FZKA and GFTN, a process involving the mitochondria and the Bcl-2 family. And Bcl-2 family was involved in this process. Interestingly, STAT3 plays a critical role on mediating the above process. Last but not the least, the enhanced effect of cell apoptosis induction of GFTN by FZKA was validated in animal model. Conclusion: Our findings conclude that Fuzheng Kang-Ai decoction enhances the effect of GFTN-induced cell apoptosis in lung cancer through the mitochondrial pathway, providing a novel molecular mechanism by which FZKA sensitizes to GFTN by delaying drug resistance in treating lung cancer patients.

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“…This study provided an explanation for the decoction’s efficacy in terms of augmenting T-cell activity and killer T-cell function, but failed to characterize the specific molecular mechanism. Another study investigated another kind of TCM, Fuzheng Kang-Ai Decoction (indicated for supporting the body and combating cancer) as an adjunct treatment option in lung cancer, where the anti-cancer effect of this decoction was ascribed to suppression of tumor cell growth via Akt-dependent repression of p65 and downregulation of MUC1 [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

Molecular targets of Yangyin Fuzheng Jiedu Prescription in the treatment of hepatocellular carcinoma based on network pharmacology analysis

et al. 2020

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Background Yangyin Fuzheng Jiedu Prescription (YFJP) is a traditional Chinese medicine (TCM) indicated for the treatment of hepatocellular carcinoma (HCC). Its potential targets and molecular mechanisms are not clear. Therefore, this study intends to explore the molecular mechanism of YFJP based on network pharmacology analysis and in vitro validation. Methods and results Through univariate and multivariate analyses and survival analysis in HCC patients with or without YFJP treatment we found that drinking alcohol, alfafeto protein ≥ 400 ng/l, baseline portal vein tumor thrombus and total bilirubin level ≥ 18.8 μM) were independent risk factors for poor prognosis, while red blood cell count ≥ 4 × 109/l and TCM treatment were independent protective factors. Besides, YFJP prolonged the cumulative survival of HCC patients. Using online pharmacological methods, we obtained 58 relevant compounds and molecular 53 targets. By using scratch test, Transwell assay, EdU assay, and TUNEL staining, we found that YFJP-containing serum repressed the migration, invasion and proliferation of HCC cells in vitro, and induced cell apoptosis. Moreover, YFJP diminished the gene expression of TP53, CCND1, p-EGFR, EGF, VEGFA, JUN, IL6, COX-2, AKT1, and MAPK1 in HCC cells, but elevated the expression of ESR1 and CASP3. Conclusions Taken together, results showed that YFJP attenuated HCC progression through mediating effects on HCC-related genes.

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Chinese herbal medicine Fuzheng Kang-Ai decoction sensitized the effect of gefitinib on inhibition of human lung cancer cells through inactivating PI3-K/Akt -mediated suppressing MUC1 expression

Cited by 16 publications

References 52 publications

Decoction of Chinese Herbal Medicine Fuzheng Kang‐Ai Induces Lung Cancer Cell Apoptosis via STAT3/Bcl‐2/Caspase‐3 Pathway

Decoction of Chinese Herbal Medicine Fuzheng Kang‐Ai Induces Lung Cancer Cell Apoptosis via STAT3/Bcl‐2/Caspase‐3 Pathway

Fuzheng Kang-Ai decoction enhances the effect of Gefitinib-induced cell apoptosis in lung cancer through mitochondrial pathway

Molecular targets of Yangyin Fuzheng Jiedu Prescription in the treatment of hepatocellular carcinoma based on network pharmacology analysis

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