Herbal compound "Songyou Yin" reinforced the ability of interferon-alfa to inhibit the enhanced metastatic potential induced by palliative resection of hepatocellular carcinoma in nude mice

Abstract

BackgroundLiver resection is a widely accepted treatment for hepatocellular carcinoma (HCC). Our previous clinical study showed that the rate of palliative resection was 34.0% (1958-2008, 2754 of 8107). However, the influence of palliative resection on tumor metastasis remains controversial. The present study was conducted to evaluate the effect of palliative resection on residual HCC and to explore interventional approaches.MethodsPalliative resection was done in an orthotopic nude mice model of HCC (MHCC97H) with high metastatic potential. Tumor growth, invasion, metastasis, lifespan, and some molecular alterations were examined in vivo and in vitro. Mice that underwent palliative resection were treated with the Chinese herbal compound "Songyou Yin," interferon-alfa-1b (IFN-α), or their combination to assess their effects.ResultsIn the palliative resection group, the number of lung metastatic nodules increased markedly as compared to the sham operation group (14.3 ± 4.7 versus 8.7 ± 3.6, P < 0.05); tumor matrix metalloproteinase 2 (MMP2) activity was elevated by 1.4-fold, with up-regulation of vascular endothelial growth factor (VEGF) and down-regulation of tissue inhibitor of metalloproteinase 2 (TIMP2). The sera of mice undergoing palliative resection significantly enhanced cell invasiveness by 1.3-fold. After treatment, tumor volume was 1205.2 ± 581.3 mm3, 724.9 ± 337.6 mm3, 507.6 ± 367.0 mm3, and 245.3 ± 181.2 mm3 in the control, "Songyou Yin," IFN-α, and combination groups, respectively. The combined therapy noticeably decreased the MMP2/TIMP2 ratio and prolonged the lifespan by 42.2%. Moreover, a significant (P < 0.001) reduction of microvessel density was found: 43.6 ± 8.5, 34.5 ± 5.9, 23.5 ± 5.6, and 18.2 ± 8.0 in the control and treatment groups, respectively.ConclusionPalliative resection-stimulated HCC metastasis may occur, in part, by up-regulation of VEGF and MMP2/TIMP2. "Songyou Yin" reinforced the ability of IFN-α to inhibit the metastasis-enhancing potential induced by palliative resection, which indicated its potential postoperative use in patients with HCC.

Tanshinone IIA inhibits metastasis after palliative resection of hepatocellular carcinoma and prolongs survival in part via vascular normalization

“…Some of these effects could include vessel normalization. We have reported that an herbal formula, Songyou Yin, can attenuate HCC metastases [17], and S. miltiorrhiza is one of the five constituents of the formula [18]. Tan IIA exhibits direct vasoactive [19,20] and certain antitumor properties [21].…”

Elevated MTSS1 expression associated with metastasis and poor prognosis of residual hepatitis B-related hepatocellular carcinoma

“…Our follow-up research suggests that HCC patients treated with palliative hepatectomy suffered from dramatically worsened metastases, suggesting that palliative hepatectomy enhances the metastatic potential of residual HCC. Although surgery is associated with tumor suppression and prolonged survival in a few cases [ 4 ], increasing number of reports indicate that hepatic resection exacerbates tumor growth and triggers tumor metastasis [ 5 – 7 ]. We found that palliative resection enhances the metastatic potential of residual HCC [ 5 ].…”

“…Although surgery is associated with tumor suppression and prolonged survival in a few cases [ 4 ], increasing number of reports indicate that hepatic resection exacerbates tumor growth and triggers tumor metastasis [ 5 – 7 ]. We found that palliative resection enhances the metastatic potential of residual HCC [ 5 ]. The present study sought to explore the underlying molecular mechanism of this metastasis-enhancing effect.…”

Su Yang Decoction induces human colon carcinoma cell apoptosis by activating caspases

“…SYD is similar in composition to other prescriptions of Chinese herbal compounds. For example, Songyou Yin has been reported to inhibit tumor growth and prolong survival in nude mice bearing a human hepatocellular carcinoma xenograft with high metastatic potential (16,17), however its composition is unknown. It has been reported that SYD comprises two cruciferous vegetable species with some bioactive constituents that exhibit antitumor properties (4,18).…”