Abstract
ObjectiveThe 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.MethodsSixty 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.ResultsPPI, 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).ConclusionPPI 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.
Highlights
Gastric cancer remains one of the leading causes of cancer death worldwide [1,2]
Each tumor tissue was divided into two parts once it removed in the surgery: (1) one part was kept in 4uC Hanks’ balanced salt solution with 1% penicillin/streptomycin and detected chemosensitivity in vitro by histoculture drug response assay (HDRA); (2) the rest part was left in formalin and made into formalin-fixed paraffin-embedded (FFPE) tumor blocks for pathological observation and gene detection
Since the anticancer efficiency of polyphyllin I (PPI) and EVO alone were not as significant as therapeutic agents, we further studied their effects on promotion of anticancer efficiency of therapeutic agents, and on reverse of chemoresistance on another 20 samples
Summary
Gastric cancer remains one of the leading causes of cancer death worldwide [1,2]. The standard first-line chemotherapy regimen for locally advanced or metastatic gastric cancer is platinum (cisplatin or oxaliplatin, Pt) and 5-FU combined with other drugs, including docetaxel and irinotecan (CPT-11) [3]; median survival remains meager – around one year. Development of novel methods and potential anticancer drugs may improve the response rate and efficiency. In China, the rhizome of P. polyphylla, known as Chong-Lou, is reported to have effects on many tumor cells and xenografts, including the pancreas, urinary bladder, breast cancer, liver tumor and lung cancer, showing strong anticancer effects in previous studies[4,5,6,7]
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