Publication date: March 2018
Source:Biomedicine & Pharmacotherapy, Volume 99
Author(s): Qin Pan, Rong Liu, Hasina Banu, Liang Ma, Hui Li
Isoprenylcysteine carboxylmethyltransferase (Icmt) catalyzes the last step of post-translational protein prenylation, which is essential for the stability and proper functions of many oncogenic proteins, such as Ras. Despite extensive studies on the roles of Icmt in tumor transformation and progression, little is known on the involvement ofIcmt in the development of tumor resistance to chemotherapy. Here we show the upregulation of Icmt as a persistent response to chemotherapy in cervical cancer cells. In-depth functional analysis demonstrated that Icmt inhibition significantly inhibited growth, induced apoptosis and augmented the inhibitory effects of chemotherapy drugs in cervical cancer in cell culture system and xenograft mouse model. Importantly, combination of Icmt specific inhibitor cysmethynil with doxorubicin or paclitaxel at sublethal concentration achieved almost full inhibition of tumor cell growth and survival. The remarkable synergy between chemotherapy drugs and Icmt inhibition in cervical cancer cells is likely due to the additional suppression of Ras and its downstream signaling pathways. We are the first to demonstrate the contribution of Icmt in tumor cells in response to chemotherapy. Our work also highlights Icmt inhibition as a sensitizing strategy for the treatment of cervical cancer or other Ras-driven tumors.
http://ift.tt/2mXLk6R
Σφακιανάκης Αλέξανδρος
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5 Άγιος Νικόλαος
Κρήτη 72100
00302841026182
00306932607174
alsfakia@gmail.com
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Σάββατο 20 Ιανουαρίου 2018
Inhibition of isoprenylcysteine carboxylmethyltransferase sensitizes common chemotherapies in cervical cancer via Ras-dependent pathway
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- Prevalence of technical errors and periapical lesi...
- Combined treatment of contaminated soil with a bac...
- Is trade openness good for environment in South Ko...
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- The effect of caregiver-delivered social-communica...
- Breaking paradigms in severe epistaxis: the import...
- Pictorial atlas of symptomatic accessory ossicles ...
- The value of FDG PET/CT for follow-up of patients ...
- Sparse domain approaches in dynamic SPECT imaging ...
- Development of a clinically feasible [11C]PE2I PET...
- Simplified estimation of binding parameters based ...
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- Intratidal Analysis of Intraoperative Respiratory ...
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- Overall Survival of Papillary Thyroid Carcinoma Pa...
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- The past and future of 'reported outcomes' in stud...
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