Synergistic anticancer effects of polyphyllin I and evodiamine on freshly-removed human gastric tumors.

ABSTRACT:

Objective

The present study was designed to examine the anticancer effect of Traditional Chinese Medicine of polyphyllin I (PPI) and evodiamine (EVO) on freshly-removed gastric tumor tissues.

Methods

Sixty freshly-removed gastric tumor tissues were collected. Their sensitivity to PPI, EVO, platinum (Pt), 5-FU, irinotecan (CPT-11) were determined by histoculture drug response assay (HDRA). Those samples were also formalin-fixed and paraffin-embedded, which were used to examine the mRNA expression levels of aprataxin(APTX), excision repair cross-complementing 1(ERCC1), thymidylate synthase(TS) and topoisomerase I(TOPO1) by quantitative RT-PCR. The association of the gene expression levels and in vitro sensitivity were analyzed.

Results

PPI, EVO, Pt, 5-FU and CPT-11 had anticancer effects on the freshly-removed gastric tumor tissues with average inhibition rates of 20.64%±14.25% for PPI, 21.14%±13.43% for EVO, 50.57%±22.37% for Pt, 53.54%±22.03% for 5-FU, and 39.33%±24.79% for CPT-11, respectively. Combination of PPI and Pt, EVO and Pt, EVO and 5-FU had higher inhibition rates than any single drug of them (P<0.001, P?=?0.028, P?=?0.017, respectively). The mRNA expression levels of ERCC1 were correlated with Pt sensitivity (rho?=?-0.645, P<0.001); the mRNA expression levels of TS were correlated with 5-FU sensitivity (rho?=?-0.803, P<0.001). There were also weak but significant correlations between APTX mRNA expression levels and CPT-11 sensitivity (rho?=?-0.376, P?=?0.017) or EVO sensitivity (rho?=?-0.322, P?=?0.036). ERCC1 mRNA expression levels was markedly suppressed by the presentation of PPI (P?=?0.001) and slightly suppressed by the presentation of EVO (P?=?0.04); whereas, TS mRNA expression levels was markedly decreased by the presentation of EVO (P?=?0.017) and slightly decreased by the presentation of PPI (P?=?0.047).

Conclusion

PPI and EVO both could inhibit the activity of freshly-removed gastric tumor, and they could enhance the anticancer effect of Pt and 5-FU by reducing the mRNA expression levels of ERCC1 and TS.

SUBMITTER: Yue G 

PROVIDER: S-EPMC3676398 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature