Sequence‑dependent effect of gemcitabine and cisplatin on A549 non‑small‑cell lung cancer cells

Tang,Yu; Wang,Yan; Teng,Xiuzhi

doi:10.3892/mmr.2013.1495

Sequence‑dependent effect of gemcitabine and cisplatin on A549 non‑small‑cell lung cancer cells

Authors:
- Yu Tang
- Yan Wang
- Xiuzhi Teng
View Affiliations

Affiliations: Department of Internal Medicine, Liaoning Tumor Hospital, Shenyang, Liaoning 110042, P.R. China, Department of Surgery, Center Hospital of Liaoning Electric Power, Shenyang, Liaoning 110015, P.R. China
Published online on: May 28, 2013 https://doi.org/10.3892/mmr.2013.1495
Pages: 221-226

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Cis‑diamminedichloroplatinum (cisplatin, CDDP)‑containing combination chemotherapy is commonly used for the treatment of non‑small‑cell lung cancer (NSCLC). 2',2'‑Difluorodeoxycytidine (gemcitabine, GEM), an active antineoplastic agent for NSCLC, has been previously reported to be suitable for use in combination with cisplatin in chemotherapy, since their mechanisms may be complementary. In the present study, the sequence‑dependent effects of GEM and CDDP were investigated in the NSCLC cell line, A549. Significantly increased rates of inhibition and cell cycle arrest were observed in the group treated with GEM followed by CDDP, and this treatment plan was demonstrated to represent the most efficient treatment protocol for the A549 NSCLC cell line. Results of the present study are consistent with previous studies in other cell lines and are likely to provide important insight for subsequent studies.

View Figures

View References

1	Kroep JR, Peters GJ, van Moorsel CJ, et al: Gemcitabine-cisplatin: A schedule finding study. Ann Oncol. 10:1503–1510. 1999. View Article : Google Scholar : PubMed/NCBI
2	No authors listed. Chemotherapy in non-small cell lung cancer: a meta-analysis using updated data on individual patients from 52 randomised clinical trials. Non-Small Cell Lung Cancer Collaborative Group. BMJ. 311:899–909. 1995. View Article : Google Scholar : PubMed/NCBI
3	No authors listed. Clinical practice guidelines for the treatment of unresectable non-small-cell lung cancer. Adopted on May 16, 1997 by the American Society of Clinical Oncology. J Clin Oncol. 15:2996–3018. 1997.PubMed/NCBI
4	Berghmans T, Paesmans M, Lalami Y, et al: Activity of chemotherapy and immunotherapy on malignant mesothelioma: a systematic review of the literature with meta-analysis. Lung Cancer. 38:111–121. 2002. View Article : Google Scholar : PubMed/NCBI
5	Braakhuis BJ, van Dongen GA, Vermorken JB and Snow GB: Preclinical in vivo activity of 2′,2′-difluorodeoxycytidine (Gemcitabine) against human head and neck cancer. Cancer Res. 51:211–214. 1991.
6	van Moorsel CJ, Veerman G, Bergman AM, et al: Combination chemotherapy studies with gemcitabine. Semin Oncol. 24(2 Suppl 7): S7-17–S7-23. 1997.
7	Peters GJ, Ruiz van Haperen VW, Bergman AM, et al: Preclinical combination therapy with gemcitabine and mechanisms of resistance. Semin Oncol. 23(5 Suppl 10): 16–24. 1996.PubMed/NCBI
8	Braakhuis BJ, Ruiz van Haperen VW, Welters MJ and Peters GJ: Schedule-dependent therapeutic efficacy of the combination of gemcitabine and cisplatin in head and neck cancer xenografts. Eur J Cancer. 31A:2335–2340. 1995. View Article : Google Scholar : PubMed/NCBI
9	Bergman AM, Ruiz van Haperen VW, Veerman G, et al: Synergistic interaction between cisplatin and gemcitabine in vitro. Clin Cancer Res. 2:521–530. 1996.PubMed/NCBI
10	Tsai CM, Chang KT, Chen JY, et al: Cytotoxic effects of gemcitabine-containing regimens against human non-small cell lung cancer cell lines which express different levels of p185neu. Cancer Res. 56:794–801. 1996.
11	Chou TC and Talalay P: Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regul. 22:27–55. 1984. View Article : Google Scholar : PubMed/NCBI
12	McKeage MJ: Comparative adverse effect profiles of platinum drugs. Drug Saf. 13:228–244. 1995. View Article : Google Scholar : PubMed/NCBI
13	Bunn PA Jr: Chemotherapy for advanced non-small-cell lung cancer: who, what, when, why? J Clin Oncol. 20:23S–33S. 2002.PubMed/NCBI
14	Voigt W, Bulankin A, Müller T, et al: Schedule-dependent antagonism of gemcitabine and cisplatin in human anaplastic thyroid cancer cell lines. Clin Cancer Res. 6:2087–2093. 2000.PubMed/NCBI
15	van Moorsel CJ, Pinedo HM, Veerman G, et al: Scheduling of gemcitabine and cisplatin in Lewis lung tumour bearing mice. Eur J Cancer. 35:808–814. 1999.PubMed/NCBI
16	Crinò L, Scagliotti G, Marangolo M, et al: Cisplatin-gemcitabine combination in advanced non-small-cell lungcancer: a phase II study. J Clin Oncol. 15:297–303. 1997.
17	Zanellato I, Boidi CD, Lingua G, et al: In vitro anti-mesothelioma activity of cisplatin-gemcitabine combinations: evidence for sequence-dependent effects. Cancer Chemother Pharmacol. 67:265–273. 2010. View Article : Google Scholar : PubMed/NCBI
18	Voigt W, Bulankin A, Müller T, et al: Schedule-dependent antagonism of gemcitabine and cisplatin in human anaplastic thyroid cancer cell lines. Clin Cancer Res. 6:2087–2093. 2000.PubMed/NCBI
19	Jackson RC: Amphibolic drug combinations: the design of selective antimetabolite protocols based upon the kinetic properties of multienzyme systems. Cancer Res. 53:3998–4003. 1993.PubMed/NCBI
20	Eastman A: The formation, isolation and characterization of DNA adducts produced by anticancer platinum complexes. Pharmacol Ther. 34:155–166. 1987. View Article : Google Scholar : PubMed/NCBI
21	Bunch RT and Eastman A: 7-Hydroxystaurosporine (UCN-01) causes redistribution of proliferating cell nuclear antigen and abrogates cisplatin-induced S-phase arrest in Chinese hamster ovary cells. Cell Growth Differ. 8:779–788. 1997.
22	Karagiannis TC and El-Osta A: Double-strand breaks: signaling pathways and repair mechanisms. Cell Mol Life Sci. 61:2137–2147. 2004.PubMed/NCBI
23	Bergstralh DT and Sekelsky J: Interstrand crosslink repair: can XPF-ERCC1 be let off the hook? Trends Genet. 24:70–76. 2008. View Article : Google Scholar : PubMed/NCBI
24	Pérol M, Chouaid C, Pérol D, et al: Randomized, phase III study of gemcitabine or erlotinib maintenance therapy versus observation, with predefined second-line treatment, after cisplatin-gemcitabine induction chemotherapy in advanced non-small-cell lung cancer. J Clin Oncol. 30:3516–3524. 2012.
25	Hida T, Ogawa S, Park JC, et al: Gefitinib for the treatment of non-small-cell lung cancer. Expert Rev Anticancer Ther. 9:17–35. 2009. View Article : Google Scholar : PubMed/NCBI
26	Ozaki K, Kishikawa F, Tanaka M, et al: Histone deacetylase inhibitors enhance the chemosensitivity of tumor cells with cross-resistance to a wide range of DNA-damaging drugs. Cancer Sci. 99:376–384. 2008. View Article : Google Scholar : PubMed/NCBI
27	Donadelli M, Costanzo C, Beghelli S, et al: Synergistic inhibition of pancreatic adenocarcinoma cell growth by trichostatin A and gemcitabine. Biochim Biophys Acta. 1773:1095–1106. 2007. View Article : Google Scholar : PubMed/NCBI