Connexin 26 induces growth suppression, apoptosis and increased efficacy of doxorubicin in prostate cancer cells.
Connexin 26 (Cx26) encodes a gap junction protein and is a putative tumor suppressor gene. We evaluated the effect of forced expression of Cx26 on three human prostate cancer cell lines, PC-3, LNCap, and DU-145. The three cell lines were infected with a Cx26 adenovirus vector (Ad-Cx26) or a control vector or were mock infected. We tested cell growth, cell cycle, apoptosis, and the efficacy of combined treatment with doxorubicin. Ad-Cx26 infection suppressed the growth of all the cell lines compared with controls and induced cell cycle arrest at the G2/M phase and apoptosis. Ad-Cx26 decreased the expression of Bcl-2. LNCaP cell growth was dramatically suppressed by Ad-Cx26 alone. PC-3 and DU-145 had greater growth suppression with combined gene therapy and chemotherapy than with either Ad-Cx26 or doxorubicin alone. Forced expression of Cx26 suppresses the growth of prostate cancer cells and decreases the expression of Bcl-2. Combining Cx26 gene therapy with doxorubicin results in greater growth suppression.
Tanaka
Motoyoshi
M
Department of Urology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Grossman
H Barton
HB
D000970:Antineoplastic Agents / Q000633:toxicity; D017209:Apoptosis / Q000502:physiology*; D002455:Cell Division / Q000502:physiology*; D045744:Cell Line, Tumor; D000072259:Connexin 26; D017630:Connexins / Q000502:physiology*; D004317:Doxorubicin / Q000633:toxicity*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D015316:Genetic Therapy; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics
D000970:Antineoplastic Agents; D017630:Connexins; C000607042:GJB2 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D000072259:Connexin 26; D004317:Doxorubicin