title: NaHCO3enhances the antitumor activities of cytokine-induced killer cells against hepatocellular carcinoma HepG2 cells.
abstract: The extracellular pH is lower inside solid tumors than in normal tissue. The acidic environment inhibits the cytotoxicity of lymphocytesin vitroand promotes tumor cell invasion. In the present study, bothin vitroandin vivoexperiments were conducted to investigate how NaHCO3would affect the antitumor activities of cytokine-induced killer (CIK) cells against hepatocellular carcinoma (HCC) cells. For thein vitroexperiments, HepG2 cells were cultured at pH 6.5 and 7.4 in the presence of CIK cells or CIK cell-conditioned medium (CMCIK). For thein vivoexperiments, nude mice were xenografted with HepG2-luc cells and divided into four groups: i) CIK cells injection plus NaHCO3feeding; ii) CIK cells injection plus drinking water feeding; iii) normal saline injection plus NaHCO3feeding; and iv) normal saline injection plus drinking water feeding. The results indicated that the viability and growth rate of HepG2 cells were remarkably suppressed when co-cultured with CIK cells or CMCIKat pH 7.4 compared with those of HepG2 cells cultured under the same conditions but at pH 6.5. In the xenograft study, a marked synergistic antitumor effect of the combined therapy was observed. NaHCO3feeding augmented the infiltration of cluster of differentiation 3-positive T lymphocytes into the tumor mass. Taken together, these data strongly suggest that the antitumor activities of CIK cells against HepG2 cells were negatively affected by the acidic environment inside the tumors, and neutralizing the pH (for example, via NaHCO3administration), could therefore reduce or eliminate this influence. In addition, it should be recommended that oncologists routinely prescribe soda water to their patients, particularly during CIK cell therapy.
authors.affiliation: Hubei Key Laboratory of Embryonic Stem Cell Research, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
authors.forename: Ya Hong
authors.initials: YH
authors.lastname: Yuan
authors.affiliation: Department of Gastroenterology, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
authors.forename: Chun Fang
authors.initials: CF
authors.lastname: Zhou
authors.affiliation: Department of Neurology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Yuan
authors.affiliation: Department of Infectious Diseases, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan, Hubei 430000, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.affiliation: Hubei Key Laboratory of Embryonic Stem Cell Research, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
authors.forename: Xing Rong
authors.initials: XR
authors.lastname: Guo
authors.affiliation: Hubei Key Laboratory of Embryonic Stem Cell Research, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
authors.forename: Xiao Li
authors.initials: XL
authors.lastname: Wang
authors.affiliation: Hubei Key Laboratory of Embryonic Stem Cell Research, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Infectious Diseases, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan, Hubei 430000, P.R. China.
authors.forename: Xiao Nan
authors.initials: XN
authors.lastname: Wang
authors.affiliation: Hubei Key Laboratory of Embryonic Stem Cell Research, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
authors.forename: Dong Sheng
authors.initials: DS
authors.lastname: Li
authors.affiliation: Hubei Key Laboratory of Embryonic Stem Cell Research, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
authors.forename: Han Jun
authors.initials: HJ
authors.lastname: Tu
keywords: HepG2; NaHCO3; acidic microenvironment; cytokine-induced killer cells; extracellular pH