Sorafenib combined with gemcitabine in EGFR-TKI-resistant human lung cancer cells

Li, Jing; Pan, Yueyin; Zhang, Ying

doi:10.3892/ol.2012.958

Cited by 5 publications

(4 citation statements)

References 21 publications

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“…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). Based on the findings of this study, we offer novel information regarding the efficacy of sorafenib in combination with bufalin for lung cancer therapy.…”

Section: Discussionsupporting

confidence: 52%

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: Discussionsupporting

confidence: 52%

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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“…In conclusion, sorafenib inhibited the proliferation of A549/DDP cisplatin-resistant lung adenocarcinoma cells in a time-and concentration-dependent manner. Sorafenib also induces apoptosis and reduces the invasiveness of A549/DDP cells, which provided scientific experimental evidence for the theoretical basis of the application of sorafenib in the subsequent treatment of cisplatin-resistant lung cancer and offers a novel and effective strategy for further treatment of advanced lung cancer (13)(14)(15).…”

Section: Discussionmentioning

confidence: 94%

Therapeutic effects of sorafenib on the A549/DDP human lung adenocarcinoma cell line in vitro

Chen

Wang

et al. 2014

Molecular Medicine Reports

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The aim of the present study was to observe the effects of sorafenib on the proliferation, apoptosis and invasion of A549/DDP cisplatin-resistant lung adenocarcinoma cells cultured in vitro. The A549/DDP cisplatin-resistant lung adenocarcinoma cell strain was cultured in vitro, the cell culture group incubated in culture medium only was set as the control group (Group S0) and the four concentration gradients of sorafenib were added to the culture groups as the experimental groups: S1, 2 µmol/l; S2, 4 µmol/l; S3, 8 µmol/l; and S4, 16 µmol/l. The MTT assay was used to determine the growth inhibition rate of the cells, which were respectively subjected to sorafenib treatment for 24, 48 and 72 h. Flow cytometry was used to determine the rate of apoptosis of cells in each group following sorafenib treatment for 72 h. Furthermore, the Transwell invasion experiment was used to determine the effect on A549/DDP cell invasion following sorafenib treatment for 24 h. Based on the MTT assay, it was found that the inhibition rates of A549/DDP cisplatin-resistant lung adenocarcinoma cells in groups S1-4 following sorafenib treatment for 24 h were 4.58±2.82, 14.93±2.62, 37.58±7.13 and 58.39±8.15%, respectively. For 48 h, inhibition rates in S1-4 were 14.98±2.93, 26.28±7.31, 63.00±3.05 and 78.84±3.96%, respectively, and for 72 h, inhibition rates were 18.80±2.82, 32.71±2.55, 75.51±4.73 and 87.50±3.36%, respectively. The difference in the inhibition rates of cells among the experimental groups for the same incubation time showed statistical significance (P<0.05). Flow cytometric analysis indicated that the rate of apoptosis in the control group was 8.88±0.81% following sorafenib treatment for 72 h, and the rates of apoptosis in groups S1-4 were, 12.84±0.24, 17.27±0.78, 21.98±0.75 and 49.67±1.38%, respectively. The rate of apoptosis in each experimental group was higher compared with that in the control group (P<0.05). The difference in the rate of apoptosis among the experimental groups was statistically significant (P<0.05). The Transwell assay showed that the number of cells permeating the septum in the control group was 82.7±2.3/high power lens (HP), while the average number of cells permeating septum in groups S1-4 following treatment with sorafenib for 24 h was 58.2±2.5, 41.3±1.3, 22.6±2.1 and 14.7±1.1/HP, which was significantly lower compared with the control group. The number of cells permeating the septum in each experimental group decreased with the enhancement of the concentration gradient. The differences were statistically significant (P<0.05). In conclusion, sorafenib inhibits the proliferation of A549/DDP cisplatin‑resistant lung adenocarcinoma cells in a time‑ and concentration‑dependent manner. In addition, sorafenib induces apoptosis in A549/DDP cisplatin‑resistant lung adenocarcinoma cells, thus reducing their invasiveness.

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“…It can damage DNA and cause cell death which is suitable for nonsmall cell lung cancer. [53] Li et al established lung cancer cell lines against EGFR-TKIs: A549, H1666, and H1975 and treated them with sorafenib and gemcitabine as a single agent for 72 h. In A549 and H1666 cells, sorafenib and gemcitabine have a synergistic effect, and the expression levels of p-AKT, p-ERK, and Bcl-2 are reduced, effectively inhibiting tumors.…”

Section: Targeting Raf To Overcome the Resistance Of Egfr-tkismentioning

confidence: 99%

EGFR TKIs Combinding the inhibition of RAS-ERK signaling in NSCLC Treatment

Wang¹,

Li²,

Ma³

et al. 2021

J Clin Res Oncol

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Epidermal growth factor receptor (EGFR) mutations and EGFR overexpression have become the key factor to the occurrence of non-small cell lung cancer (NSCLC). EGFR tyrosine-protein kinase inhibitors (EGRR-Tyrosine Kinase Inhibitors, EGFR-TKIs) were used in clinic to treat NSCLC by blocking the EGFR signaling pathway. Due to the existence of rare EGFR mutations and secondary mutations under drug load, the first generation, second generation, and third generation of EGFR TKIs have been used in clinical practice. In addition, EGFR secondary mutation and abnormal activation of EGFR downstream signaling molecules or bypass signaling pathways are the reasons for NSCLC resistance to EGFR TKIs. The combination of EGFR TKIs and EGFR downstream signal molecule inhibitors can improve the efficiency of targeted therapy for NSCLC. Based on clarifying the mechanism of resistance of NSCLC to EGFR TKIs, this paper introduces new inhibitors targeting RAS-ERK signaling downstream of EGFR. This paper also reviews progresses in a combination of EGFR TKIs and downstream signal molecule inhibitors in the treatment of NSCLC.

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Sorafenib combined with gemcitabine in EGFR-TKI-resistant human lung cancer cells

Cited by 5 publications

References 21 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

Therapeutic effects of sorafenib on the A549/DDP human lung adenocarcinoma cell line in vitro

EGFR TKIs Combinding the inhibition of RAS-ERK signaling in NSCLC Treatment

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