Combination treatment of gemcitabine and sorafenib exerts a synergistic inhibitory effect on non‑small cell lung cancer in�vitro and in�vivo via the epithelial‑to‑mesenchymal transition process

Jiang, Shanshan; Wang, Rong; Zhang, Xuan; Wu, Feihua; Li, Shengnan; Yuan, Yongfang

doi:10.3892/ol.2020.11536

Cited by 5 publications

(6 citation statements)

References 45 publications

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“…Sorafenib has been previously used in combination with another clinical anti-cancer drug, betulinic acid, to treat NSCLC cells (36). Besides, a synergistic inhibitory effect of the sorafenib and gemcitabine combination treatment on NSCLC cells has been found in vitro and in vivo (37). Another study has shown that the combination therapy increases cytotoxic efficiency in lung cancer cells with EGFR-TKI-resistance (38).…”

Section: Discussionmentioning

confidence: 95%

Combination Treatment of Sorafenib and Bufalin Induces Apoptosis in NCI-H292 Human Lung Cancer CellsIn Vitro

KUO

Liao

et al. 2022

In Vivo

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Background/Aim: Lung cancer notably contributes to tumor-associated mortality worldwide, and standard chemotherapy is used for lung cancer patients. However, its therapeutic efficacy remains unsatisfactory. This study aimed to evaluate the effects and molecular mechanisms of sorafenib and bufalin combination therapy on lung cancer cells in vitro. Materials and Methods: NCI-H292 cells were treated with sorafenib, bufalin, and sorafenib in combination with bufalin. Cell viability, ROS production, Ca 2+ release, and mitochondrial membrane potential were examined by flow cytometric assay. Annexin V/PI staining and chromatin condensation were examined by the apoptosis assays. Finally the molecular mechanism of apoptosis-associated protein expression was investigated by western blotting. Results: NCI-H292 cells treated with sorafenib in combination with bufalin showed significantly decreased viability, enhanced cellular apoptosis, and DNA condensation when compared to that with sorafenib or bufalin alone. Moreover, the combination treatment exhibited higher reactive oxygen species (ROS) production and lower mitochondrial membrane potential (ΔΨm). The combined treatment resulted in higher expression of SOD but lower catalase compared to sorafenib treatment alone. Compared to sorafenib or bufalin treatment alone, the combination treatment resulted in lower Bcl-2 expression but higher Bax, Bad, APAF-1, caspase-3, and caspase-9. Conclusion: Sorafenib in combination with bufalin shows more potent cytotoxic effects and cell apoptosis than sorafenib or bufalin treatment alone in NCI-H292 cells. The combined treatment significantly enhanced apoptotic cell death in NCI-H292 lung cancer cells by activating ROS-, mitochondria-, and caspase-signaling pathways in vitro.Cancer affects human health globally with its incidence being the most severe public issue of the 21 st century. The global number of lung cancer deaths remains high yearly (1). Lung cancers are mainly divided into two subtypes, including nonsmall cell lung cancer (NSCLC) and small cell lung cancer (SCLC). However, the NSCLC subtype occupies about 80-85% of lung cancers (2). Currently, patients undergo surgery, radiation, chemotherapy, and targeted therapy as the most commonly used strategies for lung cancer. Yet clinical outcomes of current therapies remain unsatisfactory: the 5year survival rate of lung cancer patients is less than 15% (3), and that of patients with metastatic disease is less than 10% 582 This article is freely accessible online.

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Section: Discussionmentioning

confidence: 95%

Combination Treatment of Sorafenib and Bufalin Induces Apoptosis in NCI-H292 Human Lung Cancer CellsIn Vitro

KUO

Liao

et al. 2022

In Vivo

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“…More recently, a combination of sorafenib + gemcitabine was studied using in vitro (A549, H1975, H1650 cell lines) and in vivo mice xenografts for NSCLC [ 35 ]. The results of this in vitro study indicated synergism with this combination therapy, similar to the findings of Li et al above (CI 0.65).…”

Section: Studies Of Sorafenib Efficacy In Nsclcmentioning

confidence: 99%

“…In addition, it was determined that sorafenib + gemcitabine therapy exerted anti-migration and anti-invasion effects by inhibiting epithelial-to-mesenchymal transition (EMT). In summary, this study suggests that combination therapy with sorafenib + gemcitabine may provide an effective way to inhibit metastasis via the targeting of EMT and provide better outcomes in patients with advanced NSCLC [ 35 ].…”

Section: Studies Of Sorafenib Efficacy In Nsclcmentioning

confidence: 99%

Efficacy of Sorafenib-Based Therapies for Non-Small Cell Lung Cancer

Hendrixson,

Gladkiy,

Thyagarajan

et al. 2024

Medical Sciences

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Lung cancer remains the leading cause of cancer-related deaths, with a poor prognosis. Of the two types, non-small cell lung cancer (NSCLC) is the major and most prevalent type and associated with low response rates to the current treatment options. Sorafenib, a multitargeted tyrosine kinase inhibitor used for various malignancies, gained attention for its potential efficacy in NSCLC. This review paper focuses on the findings of recent in vitro, in vivo, and clinical studies regarding the efficacy of sorafenib. Overall, sorafenib has shown definitive therapeutic potential in NSCLC cell lines, xenografts, and human subjects. Novel approaches to sorafenib delivery may improve its efficacy and should be the focus of further studies.

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“…Recently, there is a novel combination strategy of gemcitabine with sorafenib which synergistically interacts to NSCLC cells showing cytotoxicity and anti-invasive effects. Furthermore, this combination has been found to be well tolerated in patients with NSCLC [7,8].…”

Section: Introductionmentioning

confidence: 97%

FDA-Validated Ecofriendly Chromatographic Methods for Simultaneous Determination of Gemcitabine and Sorafenib: Applications to Pharmacokinetics

et al. 2022

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Combination therapy of gemcitabine and sorafenib is synergistically effective and well tolerated in patients with non-small cell lung cancer (NSCLC). In this study, the pharmacokinetic parameters of both gemcitabine and sorafenib were estimated after intra-peritoneal administration in rats using novel, green and sensitive RP-HPLC and TLC-densitometric methods where sildenafil used as an internal standard. Firstly, the developed RP-HPLC method achieved on ZORBAX Eclipse Plus C18 (4.6 mm × 150 mm, 5 μm) using a mixture of methanol: 40 mM ammonium acetate solution. On the other hand, the developed TLC-densitometric method was achieved on TLC plates using a developing system of methanol: ethyl acetate (3: 7, by volume) and scanning wave length at 260 nm. Additionally, the developed methods were validated according to FDA guidelines. Moreover, the developed methods were successfully used to study the pharmacokinetic parameters of both gemcitabine and sorafenib after administration of each drug alone and co-administration in rats. The results presented that drug–drug interaction between drugs happened when administrated together affecting the pharmacokinetic parameters of each other. The proposed methods, being ecofriendly, accurate, and sensitive, may become the corner stone for further clinical studies of the studied drugs determinations applied on humans.

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Combination treatment of gemcitabine and sorafenib exerts a synergistic inhibitory effect on non‑small cell lung cancer in�vitro and in�vivo via the epithelial‑to‑mesenchymal transition process

Cited by 5 publications

References 45 publications

Combination Treatment of Sorafenib and Bufalin Induces Apoptosis in NCI-H292 Human Lung Cancer CellsIn Vitro

Combination Treatment of Sorafenib and Bufalin Induces Apoptosis in NCI-H292 Human Lung Cancer CellsIn Vitro

Efficacy of Sorafenib-Based Therapies for Non-Small Cell Lung Cancer

FDA-Validated Ecofriendly Chromatographic Methods for Simultaneous Determination of Gemcitabine and Sorafenib: Applications to Pharmacokinetics

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