Anti-tumorigenic and Pro-apoptotic effects of CKBM on gastric cancer growth in nude mice

Abstract

Natural botanical products can be integrated with western medicine to optimize the treatment outcome, increase immune function and minimize the side effects from western drug treatment. CKBM is a combination of herbs and yeasts formulated based on traditional Chinese medicinal principles. Previous study has demonstrated that CKBM is capable of improving immune responsiveness through the induction of cytokine mediators, such as TNF-alpha and IL-6. In this study, we aimed to investigate the effect of this immunomodulatory drug on gastric cancer growth using a human xenograft model. Gastric cancer tissues were implanted subcutaneously into athymic nude mice followed by a 14-day or 28-day of CKBM treatment. Results showed that higher doses of CKBM (0.4 or 0.8 ml/mouse/day) produced a dose-dependent inhibitory effect on gastric tumor growth after 28-day drug treatment. This was associated with a decrease of cellular proliferation by 30% with concomitant increase in apoptosis by 97% in gastric tumor cells when compared with the control group. In contrast, CKBM showed no effect on angiogenesis in gastric tumors. This study demonstrates the anti-tumorigenic action of CKBM on gastric cancer probably via inhibition of cell proliferation and induction of apoptosis, and provides future potential targets of this drug candidate on cancer therapy.

Figure 1

Effect of CKBM treatment (0.2, 0.4 or 0.8 ml/mouse, given i.g. once daily) for (A) 14 days; (B) 28 days on gastric tumor growth in Balb/c nude mice (*P<0.05 when compared with the corresponding control group). Values are means ± SEM of 10-14 mice per group.

Figure 2

Effect of CKBM treatment (0.2, 0.4 or 0.8 ml/mouse, given i.g. once daily) for (A) 14 days; (B) 28 days on number of blood vessels in gastric tumors (*P<0.05, **P<0.01 when compared with the corresponding control group). Values are means ± SEM of 4-14 mice per group.

Figure 3

Effect of CKBM treatment (0.2, 0.4 or 0.8 ml/mouse, given i.g. once daily) for (A) 14 days; (B) 28 days on number of apoptotic cells in gastric tumors (*P<0.01 when compared with the control group).. Values are means ± SEM of 4-13 mice per group.

Figure 4

Effect of CKBM treatment (0.2, 0.4 or 0.8 ml/mouse, given i.g. once daily) for (A) 14 days; (B) 28 days on number of proliferative cells in gastric tumors (*P<0.05, **P<0.01 when compared with the corresponding control group). Values are means ± SEM of 4-13 mice per group.