PMID- 29115581
OWN - NLM
STAT- MEDLINE
DCOM- 20180608
LR  - 20181202
IS  - 1791-2423 (Electronic)
IS  - 1019-6439 (Linking)
VI  - 52
IP  - 1
DP  - 2018 Jan
TI  - Tramadol attenuates the sensitivity of glioblastoma to temozolomide through the 
      suppression of Cx43‑mediated gap junction intercellular communication.
PG  - 295-304
LID - 10.3892/ijo.2017.4188 [doi]
AB  - Analgesics and antineoplastic drugs are often used concurrently for cancer 
      patients. Our previous study reported that gap junctions composed of connexin32 
      (Cx32) was implicated in the effect of analgesics on cisplatin cytotoxicity. 
      However, the effect of analgesic on the most widely expressed connexin (Cx), 
      connexin43 (Cx43), and whether such effect mediates the influence on 
      chemotherapeutic efficiency remain unknown. By manipulation of Cx43 expression or 
      gap junction function, we found that there were gap junction-dependent and 
      independent effect of Cx43 on temozolomide (TMZ) sensitivity in U87 glioblastoma 
      cells. Studies on survival and apoptosis showed widely used analgesic tramadol 
      significantly reduced TMZ-induced cytotoxicity in control and negative control 
      cells but not shCx43-transfected cells. Proliferation assay demonstrated tramadol 
      suppressed TMZ-induced cytotoxicity only on high density (with gap junction 
      formation) but not on low density (without gap junction formation). Tramadol 
      inhibited dye-coupling through gap junctions between U87 cells. Tramadol 
      treatment for 72 h did not alter Cx43 expression, but decreased Cx43 
      phosphorylation accompanied with reduced p-ERK and p-JNK. Our results indicated 
      that long-term treatment with tramadol reduced TMZ cytotoxicity in U87 cells by 
      suppressing Cx43-composed gap junctions, suggesting identification and usage of 
      antinociceptive drugs which do not downregulate connexin activity should have 
      beneficial therapeutic consequences.
FAU - Wang, Lingzhi
AU  - Wang L
AD  - Department of Anaesthesia, The Second Affiliated Hospital, Guangzhou Medical 
      University, Guangzhou, Guangdong 510260, P.R. China.
FAU - Peng, Yuexia
AU  - Peng Y
AD  - Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, 
      Guangzhou, Guangdong 510080, P.R. China.
FAU - Peng, Jianxin
AU  - Peng J
AD  - Department of Hepatobiliary Surgery, Guangdong Province Traditional Chinese 
      Medicine Hospital, Guangzhou, Guangdong 510120, P.R. China.
FAU - Shao, Min
AU  - Shao M
AD  - Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, 
      Guangzhou, Guangdong 510080, P.R. China.
FAU - Ma, Li
AU  - Ma L
AD  - Department of Cardiovascular Internal Medicine, Tianyou Hospital, Wuhan 
      University of Science and Technology, Wuhan, Hubei 430064, P.R. China.
FAU - Zhu, Zhuoli
AU  - Zhu Z
AD  - Department of Anaesthesia, The Second Affiliated Hospital, Guangzhou Medical 
      University, Guangzhou, Guangdong 510260, P.R. China.
FAU - Zhong, Guocheng
AU  - Zhong G
AD  - Department of Anaesthesia, The Second Affiliated Hospital, Guangzhou Medical 
      University, Guangzhou, Guangdong 510260, P.R. China.
FAU - Xia, Zhengyuan
AU  - Xia Z
AD  - Department of Anaesthesia, The Second Affiliated Hospital, Guangzhou Medical 
      University, Guangzhou, Guangdong 510260, P.R. China.
FAU - Huang, Huansen
AU  - Huang H
AD  - Department of Anaesthesia, The Second Affiliated Hospital, Guangzhou Medical 
      University, Guangzhou, Guangdong 510260, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20171103
PL  - Greece
TA  - Int J Oncol
JT  - International journal of oncology
JID - 9306042
RN  - 0 (Analgesics, Opioid)
RN  - 0 (Antineoplastic Agents, Alkylating)
RN  - 0 (Connexin 43)
RN  - 39J1LGJ30J (Tramadol)
RN  - 7GR28W0FJI (Dacarbazine)
RN  - YF1K15M17Y (Temozolomide)
SB  - IM
MH  - Analgesics, Opioid/pharmacology
MH  - Antineoplastic Agents, Alkylating/pharmacology
MH  - Brain Neoplasms/*drug therapy/genetics/metabolism/pathology
MH  - Cell Communication/*drug effects/genetics
MH  - Cell Line, Tumor
MH  - Connexin 43/genetics/*metabolism
MH  - Dacarbazine/administration & dosage/*analogs & derivatives/pharmacology
MH  - Drug Interactions
MH  - Gap Junctions/*drug effects/genetics
MH  - Glioblastoma/*drug therapy/genetics/metabolism/pathology
MH  - Humans
MH  - Temozolomide
MH  - Tramadol/administration & dosage/*pharmacology
MH  - Transfection
EDAT- 2017/11/09 06:00
MHDA- 2018/06/09 06:00
CRDT- 2017/11/09 06:00
PHST- 2017/07/19 00:00 [received]
PHST- 2017/10/05 00:00 [accepted]
PHST- 2017/11/09 06:00 [pubmed]
PHST- 2018/06/09 06:00 [medline]
PHST- 2017/11/09 06:00 [entrez]
AID - 10.3892/ijo.2017.4188 [doi]
PST - ppublish
SO  - Int J Oncol. 2018 Jan;52(1):295-304. doi: 10.3892/ijo.2017.4188. Epub 2017 Nov 3.