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Article

Rapamycin synergizes with low dose oxaliplatin in the HCT116 colon cancer cell line by inducing enhanced apoptosis

  • Authors:
    • Xueying Lu
    • Haibo Wei
    • Xiaojin Zhang
    • Wenxin Zheng
    • Cheng Chang
    • Jinyu Gu
  • View Affiliations / Copyright

    Affiliations: Immunology Department, Basic Medical Science College, Harbin Medical University, Heilongjiang 150081, P.R. China, Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Nangang, Harbin, Heilongjiang 150086, P.R. China
  • Pages: 643-647
    |
    Published online on: May 9, 2011
       https://doi.org/10.3892/ol.2011.299
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Abstract

The present study aimed to examine the combined effects of oxaliplatin (L‑OHP) and rapamycin (RAPA) in the HCT116 colon cancer cell line. The growth inhibitory effect was evaluated by MTT assay as a monotherapy or combination therapy. IC50 values were determined using CalcuSyn 2.0 software. To determine the interaction of the drugs, the combination index (CI) was calculated using the Chou‑Talalay method. Apoptosis was investigated using flow cytometry and Western blotting. Acridine orange staining was employed to observe morphological changes. The results showed the IC50 values of L‑OHP and RAPA to be 8.35±0.78 µM (r=0.99) and 223.44±38.10 nM (r=0.94), respectively. CI was ≤1 when L‑OHP was used at doses ranging from 1 to 5 µM plus RAPA at a dose of 10 nM, suggesting synergistic or additive effects. CI was ≥1 when 100 nM RAPA was used in combination with low‑dose L‑OHP, showing additive to antagonistic effects. The combination of L‑OHP (1 µM) and RAPA (10 nM) induced 19.76% Annexin V‑positive cells, which was found to be higher than L‑OHP (11.45%, p<0.01) or RAPA (6.89%, p<0.01) alone. The cleaved PARP protein expression levels were highest after 48 h of combination treatment. Acridine orange staining showed typical bright red Acidic vesicular organelles in the RAPA group, whereas the green condensed chromatin in the apoptotic bodies was found in both the L‑OHP and combination groups. In conclusion, at a cytostatic concentration, RAPA was found to potentiate the anti‑tumor effects of low‑dose L‑OHP in the HCT116 colon cancer cell by inducing enhanced apoptosis.
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View References

1 

Parkin DM, Bray F, Ferlay J and Pisani P: Global cancer statistics, 2002. CA Cancer J Clin. 55:74–108. 2005. View Article : Google Scholar

2 

McWhinney SR, Goldberg RM and McLeod HL: Platinum neurotoxicity pharmacogenetics. Mol Cancer Ther. 8:10–16. 2009. View Article : Google Scholar

3 

Gerber DE and Choy H: Cetuximab in combination therapy: from bench to clinic. Cancer Metastasis Rev. 29:171–180. 2010. View Article : Google Scholar : PubMed/NCBI

4 

Rodriguez J, Zarate R, Bandres E, Viudez A, Chopitea A, García-Foncillas J and Gil-Bazo I: Combining chemotherapy and targeted therapies in metastatic colorectal cancer. World J Gastroenterol. 28:5867–5876. 2007. View Article : Google Scholar

5 

Wadlow RC and Ryan DP: The role of targeted agents in preoperative chemoradiation for rectal cancer. Cancer. 116:3537–3548. 2010. View Article : Google Scholar : PubMed/NCBI

6 

Johnson SM, Gulhati P, Rampy BA, Han Y, Rychahou PG, Doan HQ, Weiss HL and Evers BM: Novel expression patterns of PI3K/Akt/mTOR signaling pathway components in colorectal cancer. J Am Coll Surg. 210:767–776. 2010. View Article : Google Scholar : PubMed/NCBI

7 

Silvestris N, Tommasi S, Petriella D, Santini D, Fistola E, Russo A, Numico G, Tonini G, Maiello E and Colucci G: The dark side of the moon: the PI3K/PTEN/AKT pathway in colo-rectal carcinoma. Oncology. 77(Suppl 1): 69–74. 2009. View Article : Google Scholar : PubMed/NCBI

8 

Merimsky O, Gorzalczany Y and Sagi-Eisenberg R: Molecular impacts of rapamycin-based drug combinations: combining rapamycin with gemcitabine or imatinib mesylate (Gleevec) in a human leiomyosarcoma model. Int J Oncol. 31:225–232. 2007.

9 

Pencreach E, Guérin E, Nicolet C, Lelong-Rebel I, Voegeli AC, Oudet P, Larsen AK, Gaub MP and Guenot D: Marked activity of irinotecan and rapamycin combination toward colon cancer cells in vivo and in vitro is mediated through cooperative modulation of the mammalian target of rapamycin/hypoxia-inducible factor-1alpha axis. Clin Cancer Res. 15:1297–1307. 2009. View Article : Google Scholar

10 

Perotti A, Locatelli A, Sessa C, Hess D, Viganò L, Capri G, Maur M, Cerny T, Cresta S, Rojo F, Albanell J, Marsoni S, Corradino I, Berk L, Rivera VM, Haluska F and Gianni L: Phase IB study of the mTOR inhibitor ridaforolimus with capecitabine. J Clin Oncol. 28:4554–4561. 2010. View Article : Google Scholar : PubMed/NCBI

11 

Houghton PJ, Morton CL, Gorlick R, Lock RB, Carol H, Reynolds CP, Kang MH, Maris JM, Keir ST, Kolb EA, Wu J, Wozniak AW, Billups CA, Rubinstein L and Smith MA: Stage 2 combination testing of rapamycin with cytotoxic agents by the Pediatric Preclinical Testing Program. Mol Cancer Ther. 9:101–112. 2010. View Article : Google Scholar : PubMed/NCBI

12 

Eisenberg-Lerner A, Bialik S, Simon HU and Kimchi A: Life and death partners: apoptosis, autophagy and the cross-talk between them. Cell Death Differ. 16:966–975. 2009. View Article : Google Scholar : PubMed/NCBI

13 

Raje N, Kumar S, Hideshima T, Ishitsuka K, Chauhan D, Mitsiades C, Podar K, Le Gouill S, Richardson P, Munshi NC, Stirling DI, Antin JH and Anderson KC: Combination of the mTOR inhibitor rapamycin and CC-5013 has synergistic activity in multiple myeloma. Blood. 104:4188–4193. 2004. View Article : Google Scholar : PubMed/NCBI

14 

Gu J, Yamamoto H, Lu X, Ngan CY, Tsujino T, Konishi K, Takemasa I, Ikeda M, Nagata H, Hashimoto S, Matsuzaki T, Sekimoto M, Takagi A and Monden M: Low-dose oxaliplatin enhances the antitumor efficacy of paclitaxel in human gastric cancer cell lines. Digestion. 74:19–27. 2006. View Article : Google Scholar : PubMed/NCBI

15 

Paglin S, Hollister T, Delohery T, Hackett N, McMahill M, Sphicas E, Domingo D and Yahalom J: A novel response of cancer cells to radiation involves autophagy and formation of acidic vesicles. Cancer Res. 61:439–444. 2001.PubMed/NCBI

16 

Park SB, Goldstein D, Lin CS, Krishnan AV, Friedlander ML and Kiernan MC: Acute abnormalities of sensory nerve function associated with oxaliplatin-induced neurotoxicity. J Clin Oncol. 27:1243–1249. 2009. View Article : Google Scholar : PubMed/NCBI

17 

Nagata Y, Takahashi A, Ohnishi K, Ota I, Ohnishi T, Tojo T and Taniguchi S: Effect of rapamycin, an mTOR inhibitor, on radiation sensitivity of lung cancer cells having different p53 gene status. Int J Oncol. 37:1001–1010. 2010. View Article : Google Scholar : PubMed/NCBI

18 

Shigematsu H, Yoshida K, Sanada Y, Osada S, Takahashi T, Wada Y, Konishi K, Okada M and Fukushima M: Rapamycin enhances chemotherapy-induced cytotoxicity by inhibiting the expressions of TS and ERK in gastric cancer cells. Int J Cancer. 126:2716–2725. 2010.PubMed/NCBI

19 

Fung AS, Wu L and Tannock IF: Concurrent and sequential administration of chemotherapy and the Mammalian target of rapamycin inhibitor temsirolimus in human cancer cells and xenografts. Clin Cancer Res. 15:5389–5395. 2009. View Article : Google Scholar : PubMed/NCBI

20 

Francis LK, Alsayed Y, Leleu X, Jia X, Singha UK, Anderson J, Timm M, Ngo H, Lu G, Huston A, Ehrlich LA, Dimmock E, Lentzsch S, Hideshima T, Roodman GD, Anderson KC and Ghobrial IM: Combination mammalian target of rapamycin inhibitor rapamycin and HSP90 inhibitor 17-allylamino-17-demethoxygeldanamycin has synergistic activity in multiple myeloma. Clin Cancer Res. 12:6826–6835. 2006. View Article : Google Scholar

21 

Mondesire WH, Jian W, Zhang H, Ensor J, Hung MC, Mills GB and Meric-Bernstam F: Targeting mammalian target of rapamycin synergistically enhances chemotherapy induced cytotoxicity in breast cancer cells. Clin Cancer Res. 10:7031–7042. 2004. View Article : Google Scholar

22 

Shafer A, Zhou C, Gehrig PA, Boggess JF and Bae-Jump VL: Rapamycin potentiates the effects of paclitaxel in endometrial cancer cells through inhibition of cell proliferation and induction of apoptosis. Int J Cancer. 126:1144–1154. 2010.PubMed/NCBI

23 

Bae-Jump VL, Zhou C, Boggess JF and Gehrig PA: Synergistic effect of rapamycin and cisplatin in endometrial cancer cells. Cancer. 115:3887–3896. 2009. View Article : Google Scholar : PubMed/NCBI

24 

Kondo Y and Kondo S: Autophagy and cancer therapy. Autophagy. 2:85–90. 2006. View Article : Google Scholar

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Copy and paste a formatted citation
Spandidos Publications style
Lu X, Wei H, Zhang X, Zheng W, Chang C and Gu J: Rapamycin synergizes with low dose oxaliplatin in the HCT116 colon cancer cell line by inducing enhanced apoptosis. Oncol Lett 2: 643-647, 2011.
APA
Lu, X., Wei, H., Zhang, X., Zheng, W., Chang, C., & Gu, J. (2011). Rapamycin synergizes with low dose oxaliplatin in the HCT116 colon cancer cell line by inducing enhanced apoptosis. Oncology Letters, 2, 643-647. https://doi.org/10.3892/ol.2011.299
MLA
Lu, X., Wei, H., Zhang, X., Zheng, W., Chang, C., Gu, J."Rapamycin synergizes with low dose oxaliplatin in the HCT116 colon cancer cell line by inducing enhanced apoptosis". Oncology Letters 2.4 (2011): 643-647.
Chicago
Lu, X., Wei, H., Zhang, X., Zheng, W., Chang, C., Gu, J."Rapamycin synergizes with low dose oxaliplatin in the HCT116 colon cancer cell line by inducing enhanced apoptosis". Oncology Letters 2, no. 4 (2011): 643-647. https://doi.org/10.3892/ol.2011.299
Copy and paste a formatted citation
x
Spandidos Publications style
Lu X, Wei H, Zhang X, Zheng W, Chang C and Gu J: Rapamycin synergizes with low dose oxaliplatin in the HCT116 colon cancer cell line by inducing enhanced apoptosis. Oncol Lett 2: 643-647, 2011.
APA
Lu, X., Wei, H., Zhang, X., Zheng, W., Chang, C., & Gu, J. (2011). Rapamycin synergizes with low dose oxaliplatin in the HCT116 colon cancer cell line by inducing enhanced apoptosis. Oncology Letters, 2, 643-647. https://doi.org/10.3892/ol.2011.299
MLA
Lu, X., Wei, H., Zhang, X., Zheng, W., Chang, C., Gu, J."Rapamycin synergizes with low dose oxaliplatin in the HCT116 colon cancer cell line by inducing enhanced apoptosis". Oncology Letters 2.4 (2011): 643-647.
Chicago
Lu, X., Wei, H., Zhang, X., Zheng, W., Chang, C., Gu, J."Rapamycin synergizes with low dose oxaliplatin in the HCT116 colon cancer cell line by inducing enhanced apoptosis". Oncology Letters 2, no. 4 (2011): 643-647. https://doi.org/10.3892/ol.2011.299
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