Cisplatin regulates the MAPK kinase pathway to induce increased expression of DNA repair gene ERCC1 and increase melanoma chemoresistance

Li, Weiling; Melton, David W.

doi:10.1038/onc.2011.426

Cited by 82 publications

(71 citation statements)

References 47 publications

(57 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Of great interest was how ILK modulated these molecules. It has been shown that the expression of ERCC1 (Li et al, 2012) and GST-π (Zhang et al, 2009) is regulated by MAPK/ ERK pathway, and the RhoE has a direct interaction with ILK (Pereira et al, 2009;Berti et al, 2011). The western blotting results confirmed that the phosphorylation of ERK was attenuated by ILK silencing, which might result in the negative regulation of ERCC1 and GST-π.…”

Section: Discussionsupporting

confidence: 63%

Role of Integrin-Linked Kinase in Multi-drug Resistance of Human Gastric Carcinoma SGC7901/DDP Cells

Song

Jiang²,

Zhao³

2012

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

Gastric carcinoma is a leading cause of cancer death in the world and multi-drug resistance (MDR) is an essential aspect of gastric carcinoma chemotherapy failure. Recent studies have shown that integrin-linked kinase (ILK) is involved in metastasis of human tumors, expression silencing of ILK inhibiting the metastasis of several types of cultured human cancer cells. However, the role and potential mechanism of ILK to reverse the multidrug resistance in human gastric carcinoma is not fully clear. In this report, we focused on roles of expression silencing of ILK in multi-drug resistance reversal of human gastric carcinoma SGC7901/DDP cells, including increased drug sensitivity to cisplatin, cell apoptosis rates, and intracellular accumulation of Rhodamine-123, and decreased mRNA and protein expression of multi-drug resistance gene (MDR1), multi-drug resistanceassociated protein (MRP1), excision repair cross-complementing gene 1 (ERCC1), glutathione S-transferase -π (GST-π) and RhoE, and transcriptional activation of AP-1 and NF-κB in ILK silenced SGC7901/DDP cells. We also found that there was a decreased level of p-Akt and p-ERK. The results indicated that ILK might be used as a potential therapeutic strategy to combat multi-drug resistance through blocking PI3K-Akt and MAPK-ERK pathways in human gastric carcinoma.

show abstract

Section: Discussionsupporting

confidence: 63%

Role of Integrin-Linked Kinase in Multi-drug Resistance of Human Gastric Carcinoma SGC7901/DDP Cells

Song

Jiang²,

Zhao³

2012

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

show abstract

“…Malignant melanoma incidence is rapidly increasing and has almost doubled in the previous decade (2). Whilst DTIC chemotherapy is the standard treatment, <20% of patients respond at all to the treatment and <5% continue to respond to long-term treatment (28,29).…”

Section: Discussionmentioning

confidence: 99%

“…At present, the 10-year survival rate of patients diagnosed with advanced (stage IV) metastatic melanoma is <10% (2), which highlights the importance of early detection and treatment. The Food and Drug Administration approved the chemotherapeutic agent dacarbazine (DTIC) for the treatment of metastatic melanoma in 1975, and it remains the only licensed chemotherapeutic agent in use today (1).…”

Section: Introductionmentioning

confidence: 99%

Combined pitavastatin and dacarbazine treatment activates apoptosis and autophagy resulting in synergistic cytotoxicity in melanoma cells

Al-Qatati

Aliwaini

2017

Oncol Lett

View full text Add to dashboard Cite

Abstract. Melanoma is an aggressive skin cancer and its incidence is increasing faster than any other type of cancer. Whilst dacarbazine (DTIC) is the standard chemotherapy for metastatic melanoma, it has limited success. Statins, including pitavastatin, have been demonstrated to have a range of anticancer effects in a number of human cancer cell lines. The present study therefore explored the anti-cancer activity of combined DTIC and pitavastatin in A375 and WM115 human melanoma cells. Cell survival assays demonstrated that combined DTIC and pitavastatin treatment resulted in synergistic cell death. Cell cycle analyses further revealed that this combined treatment resulted in a G1 cell cycle arrest, as well as a sub-G1 population, indicative of apoptosis. Activation of apoptosis was confirmed by Annexin V-fluorescein isothiocyanate/propidium iodide double-staining and an increase in the levels of active caspase 3 and cleaved poly (ADP-ribose) polymerase. Furthermore, it was demonstrated that apoptosis occurs through the intrinsic pathway, evident from the release of cytochrome c. Finally, combined DTIC and pitavastatin treatment was demonstrated to also activate autophagy as part of a cell death mechanism. The present study provides novel evidence to suggest that the combined treatment of DTIC and pitavastatin may be effective in the treatment of melanoma. IntroductionMelanoma is a particularly aggressive skin cancer and its incidence is increasing faster than any other cancer worldwide (1). At present, the 10-year survival rate of patients diagnosed with advanced (stage IV) metastatic melanoma is <10% (2), which highlights the importance of early detection and treatment. The Food and Drug Administration approved the chemotherapeutic agent dacarbazine (DTIC) for the treatment of metastatic melanoma in 1975, and it remains the only licensed chemotherapeutic agent in use today (1). DTIC is a methylating agent which causes DNA damage, cell cycle arrest and apoptosis. Despite this, only 2% of all patients with metastatic melanoma receiving this treatment demonstrate a significant response and only 11.2% demonstrate a partial response (3). Resistance to DTIC has been associated with the upregulation of pro-survival signals and anti-apoptotic molecules in cancer cells. Despite its moderate effects, DTIC continues to be the standard treatment for metastatic melanoma as no other chemotherapeutic treatment has been demonstrated to have a significantly increased chance of survival when compared with DTIC (4,5). Provided the limited efficacy of the current metastatic melanoma chemotherapies in addition to the increasing incidence of melanoma cases, there appears to be a need for the development of more effective treatment strategies.Statins are a group of drugs commonly used for the reduction of cholesterol levels (6). They work by inhibiting 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase, a critical enzyme in the mevalonate pathway, which is responsible for cholesterol synthesis (6,7). In addition, statins have been de...

show abstract

“…However, the emergence of drug resistance results in the failure of chemotherapy. Various studies have revealed that the phosphoinositide 3-kinase (PI3K), mitogen-activated protein kinases (MAPKs) pathways, Bax-like proteins, and Bcl2-like proteins are involved in cisplatin resistance [7][8][9][10]. Therefore, new strategies, such as the combination of natural products and chemotherapy agents, are needed to overcome cisplatin resistance or sensitize tumor cells to cisplatin.…”

Section: Introductionmentioning

confidence: 99%

The synergistic effect of resveratrol in combination with cisplatin on apoptosis via modulating autophagy in A549 cells

Hu¹,

Li²,

Xu³

et al. 2016

ABBS

View full text Add to dashboard Cite

Several studies have shown that combination treatment with natural products and chemotherapy agents can improve the sensitivity and cytotoxicity of chemotherapy agents. Resveratrol, a natural product, has many biological effects including antitumor and antiviral activities, as well as vascular protective effect. The aim of this study is to investigate the synergistic anticancer effect of resveratrol in combination with cisplatin and the potential anticancer mechanisms involved in A549 cells. The results obtained from Cell Counting Kit-8 and isobolographic analysis demonstrated that combination of resveratrol and cisplatin resulted in synergistic cytotoxic effects in A549 cells. Results from Hoechst staining, flow cytometry and western blot analysis suggested that resveratrol enhanced cisplatin-mediated apoptosis. Meanwhile, the changes of LC3-II and P62 levels and formation of autophagosome suggested that resveratrol in combination with cisplatin triggered autophagy. More importantly, inhibiting autophagy by 3-methyladenine markedly attenuated the apoptosis caused by combination of resveratrol and cisplatin in A549 cells. Taken together, our study provides the first evidence that resveratrol combined with cisplatin synergistically induce apoptosis via modulating autophagic cell death in A549 cells. These findings also help us to understand the role of natural products in combination with chemotherapy agents in lung cancer.

show abstract

Cisplatin regulates the MAPK kinase pathway to induce increased expression of DNA repair gene ERCC1 and increase melanoma chemoresistance

Cited by 82 publications

References 47 publications

Role of Integrin-Linked Kinase in Multi-drug Resistance of Human Gastric Carcinoma SGC7901/DDP Cells

Role of Integrin-Linked Kinase in Multi-drug Resistance of Human Gastric Carcinoma SGC7901/DDP Cells

Combined pitavastatin and dacarbazine treatment activates apoptosis and autophagy resulting in synergistic cytotoxicity in melanoma cells

The synergistic effect of resveratrol in combination with cisplatin on apoptosis via modulating autophagy in A549 cells

Contact Info

Product

Resources

About