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

Wang, Sumei; Peng, Zhiwei; Li, Wenjuan; Long, Shunqin; Xiao, Shan; Wu, Wanyin

doi:10.1186/s12935-020-01270-3

Cited by 13 publications

(9 citation statements)

References 27 publications

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“…Our previous studies have shown that FZKA inhibited the growth of NSCLC cell lines including A549, PC9, and H1975 cells [23,25]. In the present study, we further observed the effect of FZKA on NSCLC cell growth inhibition in another NSCLC cell types including H1650 and H1299 using CCK-8 assay.…”

Section: Nsclc Cell Growth Was Inhibited By Fzka In Vitrosupporting

confidence: 74%

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GPX4 Plays a Crucial Role in Fuzheng Kang’ai Decoction-Induced Non-Small Cell Lung Cancer Cell Ferroptosis

Zhao

Yang

Sheng

et al. 2022

Preprint

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Background: Fuzheng Kang’ai decoction (FZKA) has been widely used to treat Non-Small Cell Lung Cancer (NSCLC) patients in China for decades, showing definite curative effects in clinic. Recently, we found that FZKA could induce NSCLC cell ferroptosis, another type of programmed cell death (PCD), which is totally different from cell apoptosis. Therefore, in the present study, we aim to discover the exact mechanism by which FZKA induces NSCLC cell ferroptosis, which is rarely studied in Traditional Chinese Medicine (TCM). Methods: Cell counting kit-8 assay and EdU proliferation assay were performed to detect the cell viability. Cell ferroptosis triggered by FZKA was observed by performing lipid peroxidation assay, Fe2+ Ions assay, and mitochondrial ultrastructure by transmission electron microscopy. Ferroptosis inhibitors including liproxstatin-1 and UAMC 3203 were used to block ferroptosis. The ratio of GSH/GSSG was done to measure the alteration of oxidative stress. Western blot and qRT-PCR were carried out to detect the expression of SLC7A11, SLC3A2, and glutathione peroxidase 4 (GPX4) at protein and mRNA levels, respectively. Lentivirus transfection was performed to overexpress GPX4 stably. Animal model was done to verify the effect of FZKA-induced ferroptosis in NSCLC in vivo and immunohistochemistry was done to detect the expression of SLC7A11, SLC3A2 and GPX4 at protein level. Results: First of all, in vitro experiments confirmed the inhibition effect of FZKA on NSCLC cell growth. We then, for the first time, found that FZKA induced NSCLC cell ferroptosis evidently, by increasing lipid peroxidation and cellular Fe2+ Ions. Moreover, characteristic morphological changes of NSCLC cell ferroptosis was observed under transmission electron microscopy. Mechanistically, GPX4, as a key inhibitor of lipid peroxidation, was greatly suppressed by FZKA treatment both at protein and mRNA levels. Furthermore, system xc- (SLC7A11 and SLC3A2) were found to be suppressed and a decreased GSH/GSSG ratio was observed at the same time by treating with FZKA. Notably, overexpressing GPX4 reversed the effect of FZKA-induced NSCLC cell ferroptosis significantly. Finally, the above effect was validated using animal model in vivo. Conclusion: Our findings conclude that GPX4 plays a crucial role in FZKA-induced NSCLC cell ferroptosis, providing a novel molecular mechanism by which FZKA treats NSCLC.

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Section: Nsclc Cell Growth Was Inhibited By Fzka In Vitrosupporting

confidence: 74%

“…The injection volume was 10μL and the column temperature was maintained at 30°C. The e cacy of different batch of FZKA is dependable [23] .…”

Section: High Performance Liquid Chromatography (Hplc)mentioning

confidence: 99%

GPX4 Plays a Crucial Role in Fuzheng Kang’ai Decoction-Induced Non-Small Cell Lung Cancer Cell Ferroptosis

Zhao

Yang

Sheng

et al. 2022

Preprint

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“…Western blot analysis was performed as described previously ( Wang et al, 2020 ). Briefly, cells (CNE-2, H1299, and HSF) were harvested, washed and lysed with 1 × RAPI buffer.…”

Section: Methodsmentioning

confidence: 99%

Compound Kushen Injection Protects Skin From Radiation Injury via Regulating Bim

et al. 2021

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Background: Radiation-induced skin injury is a major side-effect observed in cancer patients who received radiotherapy. Thus identifying new radioprotective drugs for prevention or treatment of post-irradiation skin injury should be prompted. A large number of clinical studies have confirmed that Compound Kushen injection (CKI) can enhance efficacy and reduce toxicity of radiotherapy. The aim of this study is to confirm the effect of CKI in alleviating radiotherapy injury in the skin and explore the exact mechanism.Methods: 60 patients who met the inclusion/exclusion criteria were allocated to treatment group (CKI before radiotherapy) or control group (normal saline before radiotherapy) randomly. MTT assay, flow cytometry, Western Blot, and transient transfection were performed to detect the cell viability, cell apoptosis and Bim expression after treatment with CKI or/and radiotherapy.Results: CKI had the effect of alleviating skin injury in cancer patients who received radiotherapy in clinic. CKI induced cancer cell apoptosis when combined with irradiation (IR), while it reversed the induction of cell apoptosis by IR in human skin fibroblast (HSF) cells. And Bim, as a tumor suppressor, was induced in cancer cells but had no change in HSF cells when treated with CKI. Moreover, the above effect could be attenuated when Bim was silenced by siRNA.Conclusion: We conclude that CKI represents a promising radio-protective agent with a potential differential beneficial effect on both cancer cells (inducing apoptosis) and HSF cells (providing radio-protection via inhibiting IR-induced apoptosis), via regulating Bim. Our study uncovers a novel mechanism by which CKI inhibits human cancer cell while protects skin from radiotherapy, indicating CKI might be a promising radio-protective drug.Clinical Trial Registration: Chinese Clinical Trial Registry (www.chictr.org.cn), identifier ChiCTR2100049164.

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“…Furthermore, Dziennis in 2007 showed that phosphorylated STAT3 promotes BCL-2 transcription [ 32 ]. A different study revealed that FZKA induced lung cancer cell apoptosis involving the STAT3/BCL-2/Caspase-3 pathway [ 33 ]. In our study, we showed that knockdown of ICT1 can alter the expression of apoptosis-related genes including BCL-2, BAX, cleaved caspase-3, and cleaved caspase-9 in OS cell lines.…”

Section: Discussionmentioning

confidence: 99%

ICT1 Promotes Osteosarcoma Cell Proliferation and Inhibits Apoptosis via STAT3/BCL‐2 Pathway

Pan

Tan

Weng

et al. 2021

BioMed Research International

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Osteosarcoma (OS) is a familiar malignant bone tumor that occurs mainly in adolescents. Immature colon carcinoma transcript-1 (ICT1) is an important member of the large mitoribosomal subunit in mitochondrial ribosomes, which has been shown to be closely related to tumorigenesis. Its expression and function in OS, however, remained unclear. Here, we showed that ICT1 was significantly upregulated in OS and promoted the growth of OS cells. Mechanistically, ICT1 acted as an oncogene in OS and promoted proliferation and inhibited apoptosis of OS cells through the STAT3/BCL-2 axis. These results reveal a novel insight into the role of the ICT1/STAT3/BCL-2 axis in OS and therefore may represent a novel molecular target for novel treatments.

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

Cited by 13 publications

References 27 publications

GPX4 Plays a Crucial Role in Fuzheng Kang’ai Decoction-Induced Non-Small Cell Lung Cancer Cell Ferroptosis

GPX4 Plays a Crucial Role in Fuzheng Kang’ai Decoction-Induced Non-Small Cell Lung Cancer Cell Ferroptosis

Compound Kushen Injection Protects Skin From Radiation Injury via Regulating Bim

ICT1 Promotes Osteosarcoma Cell Proliferation and Inhibits Apoptosis via STAT3/BCL‐2 Pathway

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