Targeting the KRAS, p38α, and NF‐κB in lung adenocarcinoma cancer cells: The effect of combining RNA interferences with a chemical inhibitor

Zarredar, Habib; Pashapour, Shadi; Ansarin, Khalil; Baradaran, Behzad; Ahmadzadeh, Vahideh; Safari, Fatemeh

doi:10.1002/jcb.28357

Cited by 14 publications

(5 citation statements)

References 34 publications

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“…We also reported that dual p38 and MEK inhibition effectively impaired the tumor growth of KRAS -mutated NSCLC cells [ 94 ]. Other researchers reported similar results, showing that the dual inhibition of KRAS and p38 inhibited tumor growth in KRAS -mutated colorectal cancer cells [ 95 ] and KRAS -mutated LUAD cells [ 96 ]. These findings suggest that blocking p38 or EGFR enhances the growth-inhibitory effect of KRAS G12C inhibitors on NSCLC tumors.…”

Section: Combined Therapies Involving Targeting Of Oncogenic Kras Plus Other Targeted Drugs For Kras -Mutated Nsclcmentioning

confidence: 60%

Targeting Oncogenic KRAS in Non-Small-Cell Lung Cancer

Sunaga

Miura

Kasahara

et al. 2021

Cancers

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Recent advances in molecular biology and the resultant identification of driver oncogenes have achieved major progress in precision medicine for non-small-cell lung cancer (NSCLC). v-Ki-ras2 Kirsten rat sarcoma viral oncogene (KRAS) is the most common driver in NSCLC, and targeting KRAS is considerably important. The recent discovery of covalent KRAS G12C inhibitors offers hope for improving the prognosis of NSCLC patients, but the development of combination therapies corresponding to tumor characteristics is still required given the vast heterogeneity of KRAS-mutated NSCLC. In this review, we summarize the current understanding of KRAS mutations regarding the involvement of malignant transformation and describe the preclinical and clinical evidence for targeting KRAS-mutated NSCLC. We also discuss the mechanisms of resistance to KRAS G12C inhibitors and possible combination treatment strategies to overcome this drug resistance.

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Section: Combined Therapies Involving Targeting Of Oncogenic Kras Plus Other Targeted Drugs For Kras -Mutated Nsclcmentioning

confidence: 60%

Targeting Oncogenic KRAS in Non-Small-Cell Lung Cancer

Sunaga

Miura

Kasahara

et al. 2021

Cancers

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“…They also confirmed that suppressing of the mutant KRAS expression improved the sensitivity of the NSCLC cells to p38 inhibitor (p38V) [23]. Also, Zarredar et al indicated that combination therapy with KRAS siRNA and EGFR inhibitor (AZD8931) prevents lung tumor cell progression and induced apoptosis in the lung cell line (A549) [24]. Lin and his co-workers found that KRAS status (mutant or wild) that is important in the nuclear factor kappa light chain enhancer of activated B cells (NF-κB) activation and NF-κB was low express in KRAS knockdown SW620 cells [25].…”

Section: Discussionmentioning

confidence: 84%

Combination Therapy with KRAS and P38α siRNA Suppresses Colorectal Cancer Growth and Development in SW480 Cell Line

Kamran

Seyedrezazadeh

Shanehbandi

et al. 2021

J Gastrointest Canc

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Purpose Colorectal cancer (CRC) is one of the most prevalence malignancies in a different society with a high rate of death. The KRAS and p38α axes have critical roles in the development, migration, and growth of numerous tumors, such as colorectal malignancy. KRAS mutation acts as an oncogene in various cancers and is correlated with the poor prognosis in colorectal tumors. Also, p38α plays different roles and exhibits tissue-dependent activity. In some tissues act as an oncogene while in others act as a tumor suppressor. In this research, we try to understand the effect of the P38α and KRAS genes suppression by specific siRNAs on the SW480 cell line progression. Methods We evaluate the impact of the P38α and KRAS gene knockdown by special siRNA on the growth and development of the SW480 cell line. SW480 cell line was treated with KRAS and P38α siRNAs, and the cell viability, gene expression, migration ability, and rate of apoptosis were evaluated with MTT assay, real-time PCR, scratch test, and flow cytometry. Results After treatment of the cancer cell with KRAs and P38α siRNAs, cell viability reduced to 29.16%. Also, the expression levels of the KRAS and P38α genes reduced to 26.34% and 16.06%, respectively. Apoptosis rate after combination therapy with KRAS and P38α siRNAs increased to 72.1. Also, we found that these siRNAs suppress cell migration in SW480 cell lines. ConclusionThe current study showed that combination therapy with p38α and KRAS siRNA may be considered a novel therapy for colorectal tumor in future. KeywordsColorectal cancer • KRAS • P38 • siRNA Abbreviations siRNA Small interfering RNA KRAS Ki-ras2 Kirsten rat sarcoma virus MTT 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2-Htetrazolium bromide EGFR Epidermal growth factor receptor MAPK Mitogen activation protein kinase NF-κB Nuclear factor kappa light chain enhancer of activated B cells PP2AC Protein phosphatase 2 catalytic subunit alpha gene

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“…Numerous approaches and strategies have been used for large scale and cost-effective production of biopharmaceuticals in CHO cell line to increase the production of high-quality therapeutics. These techniques include the improvement of culture media and additive supplements [ 16 ], selection of high-producing clones [ 17 ], optimization of transcriptional activity through vector engineering [ 18 ], and gene overexpression or silencing [ 19 ] using cell line engineering [ 1 , 20 ]. Apoptosis engineering by overcoming the cell death and enhancing the time integral of the viable cell concentration has been one of the important strategies which increases the product yields [ 4 ].…”

Section: Discussionmentioning

confidence: 99%

Knockout of caspase-7 gene improves the expression of recombinant protein in CHO cell line through the cell cycle arrest in G2/M phase

Safari

Akbari

2022

Biol Res

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Background Chinese hamster ovary cell line has been used routinely as a bioproduction factory of numerous biopharmaceuticals. So far, various engineering strategies have been recruited to improve the production efficiency of this cell line such as apoptosis engineering. Previously, it is reported that the caspase-7 deficiency in CHO cells reduces the cell proliferation rate. But the effect of this reduction on the CHO cell productivity remained unclear. Hence, in the study at hand the effect of caspase-7 deficiency was assessed on the cell growth, viability and protein expression. In addition, the enzymatic activity of caspase-3 was investigated in the absence of caspase-7. Results Findings showed that in the absence of caspase-7, both cell growth and cell viability were decreased. Cell cycle analysis illustrated that the CHO knockout (CHO-KO) cells experienced a cell cycle arrest in G2/M phase. This cell cycle arrest resulted in a 1.7-fold increase in the expression of luciferase in CHO-KO cells compared to parenteral cells. Furthermore, in the apoptotic situation the enzymatic activity of caspase-3 in CHO-KO cells was approximately 3 times more than CHO-K1 cells. Conclusions These findings represented that; however, caspase-7 deficiency reduces the cell proliferation rate but the resulted cell cycle arrest leads to the enhancement of recombinant protein expression. Moreover, increasing in the caspase-3 enzymatic activity compensates the absence of caspase-7 in the caspase cascade of apoptosis.

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Targeting the KRAS, p38α, and NF‐κB in lung adenocarcinoma cancer cells: The effect of combining RNA interferences with a chemical inhibitor

Cited by 14 publications

References 34 publications

Targeting Oncogenic KRAS in Non-Small-Cell Lung Cancer

Targeting Oncogenic KRAS in Non-Small-Cell Lung Cancer

Combination Therapy with KRAS and P38α siRNA Suppresses Colorectal Cancer Growth and Development in SW480 Cell Line

Knockout of caspase-7 gene improves the expression of recombinant protein in CHO cell line through the cell cycle arrest in G2/M phase

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