Hypoxia stabilizes microtubule networks and decreases tumor cell chemosensitivity to anticancer drugs through Egr-1.
The hypoxic environment of solid tumor causes the tumor cells survive and which could protect them from death by facilitating resistance to therapy. Here, we provide evidence that hypoxia can increase tumor cell viability and proliferation through an Egr-1-dependant pathway. Hypoxia protected the microtubules from disassembly, and Egr-1 was colocalized with microtubules in different cell cycle stages. Knockdown of Egr-1 with its siRNA overcame the protection effect of hypoxia and increased the sensitivity of tumor cells to vinblastine under hypoxic conditions. Our results suggest a novel approach for increasing the sensitivity of tumor cells to chemotherapeutics that target microtubule assembly.
Peng
Wan-Xin
WX
Nanjing Normal University, China.
Pan
Fei-Yan
FY
Liu
Xiao-Jin
XJ
Ning
Shen
S
Xu
Na
N
Meng
Fan-Li
FL
Wang
Yi-Qian
YQ
Li
Chao-Jun
CJ
D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D051766:Early Growth Response Protein 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008870:Microtubules / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014747:Vinblastine / Q000494:pharmacology*
D000970:Antineoplastic Agents; D051766:Early Growth Response Protein 1; D034741:RNA, Small Interfering; D014747:Vinblastine