scholarly journals Combined Treatment of Cinobufotalin and Gefitinib Exhibits Potent Efficacy against Lung Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Youxi Han ◽  
Ronghui Ma ◽  
Guolei Cao ◽  
Hao Liu ◽  
Lili He ◽  
...  

This study aimed to evaluate the efficacy of cinobufotalin combined with gefitinib in the treatment of lung cancer. A549 cells were treated with gefitinib, cinobufotalin, or cinobufotalin plus gefitinib. MTT assay, annexin-V/PI staining and flow cytometry, TUNEL staining, DCFH-DA staining, Western blot, and real-time RT-PCR were performed to investigate the synergistic inhibitory effect of cinobufotalin combined with gefitinib on the growth of A549 cells. Results showed that cinobufotalin synergized with gefitinib displayed inhibited cell viability and enhanced apoptosis in the combination group. Cinobufotalin combined with gefitinib induced a significant enhancement in reactive oxygen species (ROS) production accompanied by cell cycle arrest in the S phase arrest, characterized by upregulation of p21 and downregulation of cyclin A, cyclin E, and CDK2. Besides, cinobufotalin plus gefitinib downregulated the levels of HGF and c-Met. In summary, cinobufotalin combined with gefitinib impedes viability and facilitates apoptosis of A549 cells, indicating that the combined therapy might be a new promising treatment for lung cancer patients who are resistant to gefitinib.

2020 ◽  
Vol 19 ◽  
pp. 153473542091143
Author(s):  
Cunzhi Lin ◽  
Xinhong Zhu ◽  
Qing Jin ◽  
Aihua Sui ◽  
Jinfeng Li ◽  
...  

Sea cucumber is a kind of food. Holothurian glycosaminoglycan (hGAG) is extracted from the body wall of the sea cucumber. Administration of hGAG and cisplatin (DDP) together to treat lung cancer was investigated. Lung adenocarcinoma A549 cells were cultured and divided into 4 groups: control group, hGAG 100 µg/mL group, DDP 3 µg/mL group, and hGAG 100 µg/mL + DDP 3 µg/mL group. Cell inhibition and apoptosis was evaluated by CCK8 and Hoechst33258 staining. Cell cycle was tested by Annexin V-FITC/PI (propidium iodide) double-staining and flow cytometry. The expression of mRNA and protein of Bcl-2, Bax, caspase-3, and survivin were detected by reverse transcriptase-polymerase chain reaction and Western blot, respectively. The results showed that hGAG combined with DDP enhanced the inhibitory effect of DDP on A549 lung cells through apoptosis pathway. The mechanism of apoptosis may be related to the reduction of Bcl-2 and survivin, as well as the ascension of Bax and caspase-3. hGAG could promote A549 cell cycle arrest in G1 and G2 phase and improve the DDP chemotherapy effects on A549 cells.


2021 ◽  
pp. 37-40

Purpose: The rapid growth, morbidity and mortality of lung cancer and the lack of effective treatment have attracted great interest from researchers to find new cancer treatments aimed at the effect of gossypine on cell proliferation and apoptosis of A549 cells. The most used of these products are flavonoids. Gossypin is a potential chemo preventive and therapeutic agent for lung cancer. Material and Method: We investigated the effect of Gossypin anticancer activity on A549 cell proliferation with MTT method, depending on dose and time. In addition, mRNA expression levels of the apoptotic markers caspase-3 (CAS-3) and caspase-9 (CAS-9) were investigated by real-time PCR. In our study, six groups were used as control, gossypin (10, 20, 40 μM), cisplatin 5 μg/mL and cisplatin 5 μg/mL+gossypin 40 μM combine concentrations. The proliferative and antiapoptotic effects of gossypin at 24, 48 and 72 hours were investigated. Results were analyzed and presented as cell viability (%). Results: In our results, it was determined that gossypin especially at a dose of 40 μM and at 72 hours showed almost as much effect on A549 cells, but the highest inhibitory effect was seen in the 40 combined group of cisplatin 5 μg / mL + gossypin. In addition, gossypin caused a significant increase in apoptosis genes (CASP-3, CASP-9) compared to control. Conclusion: Our study showed that gossypin significantly increases the chemosensitivity of cisplatin. Based on this, it is predicted that gossypin can be used as a supportive therapy that increases the effectiveness of anticancer agents. However, more detailed research should be done for this.


2020 ◽  
Vol 16 (7) ◽  
pp. 255-262
Author(s):  
David Robinson ◽  
Stephanie Hawthorne ◽  
Linda Zhao ◽  
Madelyn Hanson ◽  
Gena Kanas ◽  
...  

Aim: To report the results of a survey of USA physicians (CancerMPact) that treat non-small-cell lung cancer patients. Materials & methods: 60 physicians were surveyed. Questions covered aspects of the treatment for all stages of the disease. Results: For stage I patients, over 70% of the treatments were based on surgery. For stage II/III disease, a strong preference for combined therapy (surgery/radiation/systemic therapy) was observed. For advanced/stage IV patients, physicians used systemic therapy alone, and choosed the regimen based on histology and biomarkers. Use of PD-L1 inhibitors was highly dependent on histology and biomarkers. Conclusion: The treatment choices of non-small-cell lung cancer are increasingly complex, involve different treatment modalities and are highly dependent on histology and biomarkers, besides stage.


2020 ◽  
Vol 326 ◽  
pp. 109133 ◽  
Author(s):  
Virginia Marcia Concato ◽  
Fernanda Tomiotto-Pellissier ◽  
Taylon Felipe Silva ◽  
Manoela Daiele Gonçalves ◽  
Bruna Taciane da Silva Bortoleti ◽  
...  

2016 ◽  
Vol 44 (07) ◽  
pp. 1473-1490 ◽  
Author(s):  
Wipada Duangprompo ◽  
Kalaya Aree ◽  
Arunporn Itharat ◽  
Pintusorn Hansakul

5,6-dihydroxy-2,4-dimethoxy-9,10-dihydrophenanthrene (HMP) is an active compound isolated from the rhizome extracts of Dioscorea membranacea Pierre, a Thai medicinal plant. This study aimed to investigate the growth-inhibitory and apoptosis-inducing effects of HMP in human lung cancer A549 cells. The antiproliferative and cytotoxic effects of HMP were analyzed by a Sulforhodamine B assay. Cell division, cell cycle distribution and membrane asymmetry changes were each performed with different fluorescent dyes and then analyzed by flow cytometry. Real-time PCR and immunoblotting were used to detect cell cycle- and apoptosis-related mRNA levels and proteins, respectively. The nuclear morphology of the cells stained with DAPI and DNA fragmentation were detected by fluorescence microscopy and gel electrophoresis, respectively. The results showed that HMP exerted strong antiproliferative and cytotoxic activities in A549 cells with the highest selectivity index. It halted the cell cycle in [Formula: see text]/M phase via down-regulation of the expression levels of regulatory proteins Cdc25C, Cdk1 and cyclinB1. In addition, HMP induced early apoptotic cells with externalized phosphatidylserine and subsequent apoptotic cells in sub-[Formula: see text] phase. HMP increased caspase-3 activity and levels of the cleaved (active) form of caspase-3 whose actions were supported by the cleavage of its target PARP, nuclear condensation and DNA apoptotic ladder. Moreover, HMP significantly increased the mRNA and protein levels of proapoptotic Bax as well as promoted subsequent caspase-9 activation and BID cleavage, indicating HMP-induced apoptosis via both intrinsic and extrinsic pathways. These data support, for the first time, the potential role of HMP as a cell-cycle arrest and apoptosis-inducing agent for lung cancer treatment.


2018 ◽  
Vol 96 (1) ◽  
pp. 50-56 ◽  
Author(s):  
M.E. Abdraboh ◽  
S.H. Abdeen ◽  
M. Salama ◽  
M. El-Husseiny ◽  
Y.M. El-Sherbini ◽  
...  

Trichloroethylene (TCE) is one of the industrial toxic byproducts that now persist in the air, soil, and water. Several studies have already illustrated the toxic effect of high doses of TCE on the biological functions of several organs. This study aims to highlight the toxic impact of a low dose of TCE (1 μmol/L) on the development of rat neural stem cells (NSCs). The subventricular zones (SVZ) of rat pup’s brains were collected and minced, and the harvested cells were cultured in the presence of neural growth factors B27/N2 to develop neurospheres. The cells were then exposed to a dose of 1 μmol/L TCE for 1 or 2 weeks. The outcomes indicated a remarkable inhibitory effect of TCE on the differentiation capacity of NSCs, which was confirmed by down-regulation of the astrocyte marker GFAP The inhibitory effect of TCE on the proliferation of NSCs was identified by the reductions in neurosphere diameter, Ki67 expression, and cell cycle arrest at the G1/S phase. Immunolabelling with annexin V indicated the proapoptotic effect of TCE exposure. PCR results revealed a TCE-mediated suppression of the expression of the antioxidant enzyme SOD1. This paper illustrates, for the first time, a detailed examination of the toxic effects of an environmentally low dose of TCE on NCSs at the transcriptional, translational, and functional levels.


2004 ◽  
Vol 212 (1) ◽  
pp. 53-60 ◽  
Author(s):  
Ya-Ling Hsu ◽  
Po-Lin Kuo ◽  
Chi-Feng Liu ◽  
Chun-Ching Lin

2013 ◽  
Vol 798-799 ◽  
pp. 1018-1021
Author(s):  
Ye Xu ◽  
Ning Wang ◽  
Yan Ding ◽  
Yang Yu ◽  
Shi Bing Liu ◽  
...  

The aim of this study is to investigate the effects and mechanism of ammonium chloride (NH4Cl) on the apoptosis induced by cisplatin in human lung cancer A549 cells. MTT assay was used to detect the state of cell growth. The expressions of apoptosis related proteins were detected by Laser scanning confocal microscopy and western blot. MTT tests showed that the non-toxic dose of NH4Cl could increase the inhibition rate of A549 cells induced by cisplatin. The expression of active caspase-3 in cells treated with non-toxic dose of NH4Cl combined with cisplatin was higher than that in cells treated with cisplatin alone. Western blot analysis showed that the expressions of apoptosis related proteins were significantly increased in the combination group. These results indicate that NH4Cl can enhance the cell apoptosis induced by cisplatin in A549 cells.


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