Natural killer cells inhibit pulmonary metastasis of hepatocellular carcinoma in nude mice.

ABSTRACT

Natural killer (NK) cells have been demonstrated to inhibit tumor growth. However, the role of NK cells in the inhibition of hepatocellular carcinoma metastasis is not well understood. The present study aimed to investigate the roles that NK cells may serve in inhibiting hepatocellular carcinoma metastasis. The role of isolated NK cells in the inhibition, proliferation, migration and invasion of the hepatoma cell line, MHCC97-H, was examined in vitro. Additionally, the survival rate of NK cells labeled with carboxyfluorescein diacetate-succinimidyl ester was assessed in vivo. An orthotopic implantation model was used to evaluate the role of NK cells in suppressing MHCC97-H cells in vivo. The effect of interleukin (IL)-2 stimulation on the tumor-inhibitory role of the NK cells was measured indirectly by analyzing the expression of various NK cell receptors and activated NK cell markers. It was observed that the NK cells inhibited the proliferation, migration and invasion of the MHCC97-H cells in vitro. Furthermore, the NK cells demonstrated long-term survival in the livers of the nude mice, and inhibited lung metastasis of hepatocellular carcinoma in vivo. However, liver tumor growth was not inhibited by the NK cells. IL-2 was identified to enhance the tumor-inhibitory effect of NK cells. The present study concludes that IL-2 may enhance the antitumor activity of the NK cells, and thereby inhibit the metastases of hepatocellular carcinoma in mice.