Open Access

Novel proapoptotic agent SM-1 enhances the inhibitory effect of 5-fluorouracil on colorectal cancer cells in vitro and in vivo

  • Authors:
    • Ying Wang
    • Shoujun Yuan
    • Linna Li
    • Dexuan Yang
    • Chengwang Xu
    • Shanshan Wang
    • Danshen Zhang
  • View Affiliations

  • Published online on: April 19, 2017     https://doi.org/10.3892/ol.2017.6043
  • Pages: 4762-4768
  • Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

5-Fluorouracil (5-FU) is one of the most important agents used to treat colorectal cancer. However, the therapeutic effect of 5‑FU on colon cancer is limited. SM‑1 is a novel type of proapoptotic agent that directly activates procaspase‑3 to caspase‑3, leading to apoptosis in human cancer cells. The aim of the present study was to evaluate the antitumor effects of 5‑FU in combination with SM‑1. The human colorectal cancer cell lines HCT116 and LoVo were cultured in the presence of SM‑1 and 5‑FU. The combination of SM‑1 and 5‑FU treatment exhibited increased proliferation inhibitory effects compared with 5‑FU treatment alone in HCT116 and LoVo cells, as determined using an MTT assay. SM‑1 significantly decreased the half‑maximal inhibitory concentration of 5‑FU from 8.07±0.49 to 2.55±0.41 µmol/l in HCT116 cells, and from 7.90±0.98 to 3.14±0.81 µmol/l in LoVo cells. Similarly, the apoptotic activity was increased to 47.95 and 35.19% in HCT116 and LoVo cells, respectively, as determined using Annexin V/propidium iodide staining and flow cytometry. The combination of SM‑1 and 5‑FU treatment led to significantly increased caspase‑3 activity compared with either compound alone. The reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and western blot analysis revealed the downregulation of B‑cell lymphoma 2 and Survivin, and the upregulation of apoptosis regulator Bcl‑2‑associated X protein and cleaved poly (ADP‑ribose) polymerase in HCT116 and LoVo cells. In addition, RT‑qPCR identified downregulation of X‑linked inhibitor of apoptosis protein mRNA. 5‑FU and SM‑1 treatment in combination increased tumor proliferation inhibition in HCT116 and LoVo xenograft mouse models of colorectal cancer, compared with SM‑1 or 5‑FU treatment alone. SM‑1 significantly enhanced the antitumor activity of 5‑FU in colorectal cancer. These improved effects were due to increased activity of the apoptotic signaling pathway.
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June-2017
Volume 13 Issue 6

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Spandidos Publications style
Wang Y, Yuan S, Li L, Yang D, Xu C, Wang S and Zhang D: Novel proapoptotic agent SM-1 enhances the inhibitory effect of 5-fluorouracil on colorectal cancer cells in vitro and in vivo. Oncol Lett 13: 4762-4768, 2017
APA
Wang, Y., Yuan, S., Li, L., Yang, D., Xu, C., Wang, S., & Zhang, D. (2017). Novel proapoptotic agent SM-1 enhances the inhibitory effect of 5-fluorouracil on colorectal cancer cells in vitro and in vivo. Oncology Letters, 13, 4762-4768. https://doi.org/10.3892/ol.2017.6043
MLA
Wang, Y., Yuan, S., Li, L., Yang, D., Xu, C., Wang, S., Zhang, D."Novel proapoptotic agent SM-1 enhances the inhibitory effect of 5-fluorouracil on colorectal cancer cells in vitro and in vivo". Oncology Letters 13.6 (2017): 4762-4768.
Chicago
Wang, Y., Yuan, S., Li, L., Yang, D., Xu, C., Wang, S., Zhang, D."Novel proapoptotic agent SM-1 enhances the inhibitory effect of 5-fluorouracil on colorectal cancer cells in vitro and in vivo". Oncology Letters 13, no. 6 (2017): 4762-4768. https://doi.org/10.3892/ol.2017.6043