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NaHCO3 enhances the antitumor activities of cytokine-induced killer cells against hepatocellular carcinoma HepG2 cells

  • Authors:
    • Ya Hong Yuan
    • Chun Fang Zhou
    • Jiang Yuan
    • Li Liu
    • Xing Rong Guo
    • Xiao Li Wang
    • Yan Ding
    • Xiao Nan Wang
    • Dong Sheng Li
    • Han Jun Tu
  • View Affiliations / Copyright

    Affiliations: Hubei Key Laboratory of Embryonic Stem Cell Research, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China, Department of Gastroenterology, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China, Department of Neurology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China, Department of Infectious Diseases, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan, Hubei 430000, P.R. China
    Copyright: © Yuan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 3167-3174
    |
    Published online on: September 9, 2016
       https://doi.org/10.3892/ol.2016.5112
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Abstract

The extracellular pH is lower inside solid tumors than in normal tissue. The acidic environment inhibits the cytotoxicity of lymphocytes in vitro and promotes tumor cell invasion. In the present study, both in vitro and in vivo experiments were conducted to investigate how NaHCO3 would affect the antitumor activities of cytokine‑induced killer (CIK) cells against hepatocellular carcinoma (HCC) cells. For the in vitro experiments, HepG2 cells were cultured at pH 6.5 and 7.4 in the presence of CIK cells or CIK cell‑conditioned medium (CMCIK). For the in vivo experiments, nude mice were xenografted with HepG2‑luc cells and divided into four groups: i) CIK cells injection plus NaHCO3 feeding; ii) CIK cells injection plus drinking water feeding; iii) normal saline injection plus NaHCO3 feeding; 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 CMCIK at 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. NaHCO3 feeding 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 NaHCO3 administration), 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.
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Copy and paste a formatted citation
Spandidos Publications style
Yuan YH, Zhou CF, Yuan J, Liu L, Guo XR, Wang XL, Ding Y, Wang XN, Li DS, Tu HJ, Tu HJ, et al: NaHCO3 enhances the antitumor activities of cytokine-induced killer cells against hepatocellular carcinoma HepG2 cells. Oncol Lett 12: 3167-3174, 2016.
APA
Yuan, Y.H., Zhou, C.F., Yuan, J., Liu, L., Guo, X.R., Wang, X.L. ... Tu, H.J. (2016). NaHCO3 enhances the antitumor activities of cytokine-induced killer cells against hepatocellular carcinoma HepG2 cells. Oncology Letters, 12, 3167-3174. https://doi.org/10.3892/ol.2016.5112
MLA
Yuan, Y. H., Zhou, C. F., Yuan, J., Liu, L., Guo, X. R., Wang, X. L., Ding, Y., Wang, X. N., Li, D. S., Tu, H. J."NaHCO3 enhances the antitumor activities of cytokine-induced killer cells against hepatocellular carcinoma HepG2 cells". Oncology Letters 12.5 (2016): 3167-3174.
Chicago
Yuan, Y. H., Zhou, C. F., Yuan, J., Liu, L., Guo, X. R., Wang, X. L., Ding, Y., Wang, X. N., Li, D. S., Tu, H. J."NaHCO3 enhances the antitumor activities of cytokine-induced killer cells against hepatocellular carcinoma HepG2 cells". Oncology Letters 12, no. 5 (2016): 3167-3174. https://doi.org/10.3892/ol.2016.5112
Copy and paste a formatted citation
x
Spandidos Publications style
Yuan YH, Zhou CF, Yuan J, Liu L, Guo XR, Wang XL, Ding Y, Wang XN, Li DS, Tu HJ, Tu HJ, et al: NaHCO3 enhances the antitumor activities of cytokine-induced killer cells against hepatocellular carcinoma HepG2 cells. Oncol Lett 12: 3167-3174, 2016.
APA
Yuan, Y.H., Zhou, C.F., Yuan, J., Liu, L., Guo, X.R., Wang, X.L. ... Tu, H.J. (2016). NaHCO3 enhances the antitumor activities of cytokine-induced killer cells against hepatocellular carcinoma HepG2 cells. Oncology Letters, 12, 3167-3174. https://doi.org/10.3892/ol.2016.5112
MLA
Yuan, Y. H., Zhou, C. F., Yuan, J., Liu, L., Guo, X. R., Wang, X. L., Ding, Y., Wang, X. N., Li, D. S., Tu, H. J."NaHCO3 enhances the antitumor activities of cytokine-induced killer cells against hepatocellular carcinoma HepG2 cells". Oncology Letters 12.5 (2016): 3167-3174.
Chicago
Yuan, Y. H., Zhou, C. F., Yuan, J., Liu, L., Guo, X. R., Wang, X. L., Ding, Y., Wang, X. N., Li, D. S., Tu, H. J."NaHCO3 enhances the antitumor activities of cytokine-induced killer cells against hepatocellular carcinoma HepG2 cells". Oncology Letters 12, no. 5 (2016): 3167-3174. https://doi.org/10.3892/ol.2016.5112
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