Silencing of pkm2 increases the efficacy of docetaxel in human lung cancer xenografts in mice.
Tumor aerobic glycolysis, or the Warburg effect, plays important roles in tumor survival, growth, and metastasis. Pyruvate kinase isoenzyme M2 (PKM2) is a key enzyme that regulates aerobic glycolysis in tumor cells. Recent research has shown that PKM2 can be used as a tumor marker for diagnosis and, in particular, as a potential target for cancer therapy. We investigated the effects of combining shRNA targeting PKM2 and docetaxel on human A549 lung carcinoma cells both in vivo and in vitro. We observed that the shRNA can significantly downregulate the expression level of PKM2. The decrease of PKM2 resulted in a decrease in ATP synthesis, which caused intracellular accumulation of docetaxel. Furthermore, the combination of pshRNA-pkm2 and docetaxel inhibited tumor growth and promoted more cancer cell apoptosis both in vivo and in vitro. Our findings suggest that targeting tumor glycolysis can increase the efficacy of chemotherapy. In particular, the targeting of PKM2 could, to some extent, be a new way of reversing chemotherapy resistance to cancer therapy.
Shi
Hua-shan
HS
Department of Thoracic Oncology, Sichuan University, Chengdu, China.
Li
Dan
D
Zhang
Jing
J
Wang
Yong-sheng
YS
Yang
Li
L
Zhang
Hai-long
HL
Wang
Xian-Huo
XH
Mu
Bo
B
Wang
Wei
W
Ma
Yu
Y
Guo
Fu-chun
FC
Wei
Yu-Quan
YQ
D000255:Adenosine Triphosphate / Q000032:analysis; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D000077143:Docetaxel; D005260:Female; D020868:Gene Silencing; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D011770:Pyruvate Kinase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D034622:RNA Interference; D043823:Taxoids / Q000627:therapeutic use*; D023041:Xenograft Model Antitumor Assays
D000972:Antineoplastic Agents, Phytogenic; D043823:Taxoids; D000077143:Docetaxel; D000255:Adenosine Triphosphate; D011770:Pyruvate Kinase