Kanser konusunda yapılan çalışmalar göstermektedir ki; tümörler oksijensiz ortamda daha hızlı çoğalmakta ve daha agresif hal almaktadır. Ayrıca Hipoksik ortamın sonunda ortamda nekroz oluşturmakta ve enerji metabolizması sonucu ortamda oluşan laktik asit sayesinde de asidik ortamda yaşamaktadır.
Kanser hücrelerinin artan ATP (Enerji) ihtiyacını karşılamak için glikolizisi artar. Mitokondrial solunum hasarı ve hipoksi sonucunda tedavide kullanılan radyoterapi ve kemoterapiye karşı direnç gelişmektedir.
Hipoksi ile indüklenen faktör-1α (HIF-1 α) bir nükleer proteindir ve azalan hücre içi oksijen konsantrasyonuna cevap olarak regüle edilir. Bu nedenle bir hipoksi belirteci gibi görev yapar.
Sonuç olarak kanın oksijen taşıma kapasitesinde artış yaparak doku oksijenizasyonunun artırılmasının ne kadar önemli olduğu ortaya çıkmaktadır.
Inhibition of Glycolysis in Cancer Cells: A Novel Strategy to Overcome Drug Resistance Associated with Mitochondrial Respiratory Defect and Hypoxia
- Rui-hua Xu1,3,
- Helene Pelicano1,
- Yan Zhou1,
- Jennifer S. Carew1,
- Li Feng1,
- Kapil N. Bhalla4,
- Michael J. Keating2, and
- Peng Huang1
+Author Affiliations
- Requests for reprints:
Peng Huang, Department of Molecular Pathology, University of Texas M.D. Anderson Cancer Center, Box 89, 1515 Holcombe Boulevard, Houston, TX 77030. Phone: 713-792-7742; Fax: 713-794-4672; E-mail: phuang@mdanderson.org.
Abstract
Cancer cells generally exhibit increased glycolysis for ATP generation (the Warburg effect) due in part to mitochondrial respiration injury and hypoxia, which are frequently associated with resistance to therapeutic agents. Here, we report that inhibition of glycolysis severely depletes ATP in cancer cells, especially in clones of cancer cells with mitochondrial respiration defects, and leads to rapid dephosphorylation of the glycolysis-apoptosis integrating molecule BAD at Ser112, relocalization of BAX to mitochondria, and massive cell death. Importantly, inhibition of glycolysis effectively kills colon cancer cells and lymphoma cells in a hypoxic environment in which the cancer cells exhibit high glycolytic activity and decreased sensitivity to common anticancer agents. Depletion of ATP by glycolytic inhibition also potently induced apoptosis in multidrug-resistant cells, suggesting that deprivation of cellular energy supply may be an effective way to overcome multidrug resistance. Our study shows a promising therapeutic strategy to effectively kill cancer cells and overcome drug resistance. Because the Warburg effect and hypoxia are frequently seen in human cancers, these findings may have broad clinical implications.
Review
Nature Reviews Cancer 4, 437-447 (June 2004) | doi:10.1038/nrc1367
Exploiting tumour hypoxia in cancer treatment
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Abstract
Solid tumours contain regions at very low oxygen concentrations (hypoxia), often surrounding areas of necrosis. The cells in these hypoxic regions are resistant to both radiotherapy and chemotherapy. However, the existence of hypoxia and necrosis also provides an opportunity for tumour-selective therapy, including prodrugs activated by hypoxia, hypoxia-specific gene therapy, targeting the hypoxia-inducible factor 1 transcription factor, and recombinant anaerobic bacteria. These strategies could turn what is now an impediment into a significant advantage for cancer therapy.
Mevcut yazılı metin bilgilendirme amaçlıdır. Bilimsel verilerden elde edilmiş bilgilerdir. Konu hakkında uzman kişiler tarafından yönlendirilmeniz ve tedaviye yönelik işlemleri bir hekim kontrolünde uygulamanız veya uygulatmanız önerilir.Ankara ozon , ozon ankara , alternatif kanser tedavisi , dmso , integratif tıp , akupunktur ,
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