Establishment of a first‑line second‑line treatment model for human pulmonary adenocarcinoma

Wang,Lining; Wang,Yu; Guan,Qi; Liu,Yong; He,Tianyi; Wang,Jiaru

doi:10.3892/ol.2016.5299

Establishment of a first‑line second‑line treatment model for human pulmonary adenocarcinoma

Authors:
- Lining Wang
- Yu Wang
- Qi Guan
- Yong Liu
- Tianyi He
- Jiaru Wang
View Affiliations

Affiliations: Central Laboratory, Central Hospital Affiliated To Shenyang Medical College, Shenyang, Liaoning 110024, P.R. China, Department of Laboratory, Central Hospital Affiliated To Shenyang Medical College, Shenyang, Liaoning 110024, P.R. China, The 1st Cardiology Department, Central Hospital Affiliated To Shenyang Medical College, Shenyang, Liaoning 110024, P.R. China
Published online on: October 19, 2016 https://doi.org/10.3892/ol.2016.5299
Pages: 4461-4466
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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

Lung cancer is one of the most prevalent types of cancer in the world. Surgery, chemotherapy and radiotherapy are used clinically as treatments for numerous cancers. Due to the appearance of drug resistance, the remission rate is limited to 40‑50%. Docetaxel and pemetrexed are two drugs commonly used, and their effects in single‑phase cell culture are well known. From the pharmacological point of view, it appears rational to hypothesize that sequential therapy effects can show better outcomes compared with traditional single‑phase experiments. Considering this, the present study aimed to establish a first‑line second‑line adenocarcinoma treatment model, using the combination of cisplatin with docetaxel or pemetrexed in vitro in different sequential therapy timings. To test this, the human lung cancer A549 cell line was used. The inhibitory effect was determined by adding docetaxel following treatment with cisplatin and pemetrexed (Pem‑Doc group) and comparing this with a group in which pemetrexed was added subsequent to treatment with cisplatin and docetaxel (Doc‑Pem group). Additionally, the differences in the gene and protein expression levels of excision repair cross‑completion gene 1 (ERCC1), a gene that promotes drug resistance to cisplatin, were compared between the two groups. The present results showed that the inhibitory effect of cell proliferation in the Pem‑Doc group was increased compared with that of Doc‑Pem group, while the gene expression and protein levels of ERCC1 in the Pem‑Doc group were decreased compared with those of Doc‑Pem group. The Pem‑Doc treatment plan is more effective in inhibiting cell proliferation and in lowering the expression of the ERCC1 gene. Therefore, Pem‑Doc may be a more effective adenocarcinoma treatment.

View Figures

View References

1	Takita H, Edgerton F, Marabella P, Conway D and Harguindey S: Platinum-based combination chemotherapy in non-small cell lung carcinoma. Cancer. 48:1528–1530. 1981. View Article : Google Scholar : PubMed/NCBI
2	Belani CP: Docetaxel in combination with platinums in patients with advanced non-small-cell lung cancer. Oncology (Williston Park). 11(8): Suppl 8. S42–S45. 1997.
3	Stinchcombe TE, Borghaei H, Barker SS, Treat JA and Obasaju C: Pemetrexed with platinum combination as a backbone for targeted therapy in non-small-cell lung cancer. Clin Lung Cancer. 17:1–9. 2016. View Article : Google Scholar : PubMed/NCBI
4	Al-Farsi A and Ellis PM: Treatment paradigms for patients with metastatic non-small cell lung cancer, squamous lung cancer: First, second, and third-line. Front Oncol. 4:1572014. View Article : Google Scholar : PubMed/NCBI
5	Gatzemeier U, von Pawel J, Gottfried M, ten Velde GP, Mattson K, de Marinis F, Harper P, Salvati F, Robinet G, Lucenti A, et al: Phase III comparative study of high-dose cisplatin versus a combination of paclitaxel and cisplatin in patients with advanced non-small cell lung cancer. J Clin Oncol. 18:3390–3399. 2000.PubMed/NCBI
6	Scagliotti GV, De Marinis F, Rinaldi M, Crinò L, Gridelli C, Ricci S, Matano E, Boni C, Marangolo M, Failla G, et al: Phase III randomized trial comparing three platinum-based doublets in advanced non-small-cell lung cancer. J Clin Oncol. 20:4285–4291. 2002. View Article : Google Scholar : PubMed/NCBI
7	Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, Zhu J and Johnson DH: Eastern Cooperative Oncology Group: Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med. 346:92–98. 2002. View Article : Google Scholar : PubMed/NCBI
8	Smit EF, van Meerbeeck JP, Lianes P, Debruyne C, Legrand C, Schramel F, Smit H, Gaafar R, Biesma B, Manegold C, et al: Three-arm randomized study of two cisplatin-based regimens and paclitaxel plus gemcitabine in advanced non-small-cell lung cancer: A phase III trial of the European organisation for research and treatment of cancer lung cancer group-EORTC 08975. J Clin Oncol. 21:3909–3917. 2003. View Article : Google Scholar : PubMed/NCBI
9	Fossella F, Pereira JR, von Pawel J, Pluzanska A, Gorbounova V, Kaukel E, Mattson KV, Ramlau R, Szczesna A, Fidias P, et al: Randomized, multinational, phase III study of docetaxel plus platinum combination versus vinorelbine plus cisplatin for advanced non-small-cell lung cancer: The TAX 326 study group. J Clin Oncol. 21:3016–3024. 2003. View Article : Google Scholar : PubMed/NCBI
10	Shepherd FA, Dancey J, Ramlau R, Mattson K, Gralla R, O'Rourke M, Levitan N, Gressot L, Vincent M, Burkes R, et al: Prospective randomized trial of docetaxel versus best supportive care in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy. J Clin Oncol. 18:2095–2103. 2000.PubMed/NCBI
11	Fossella FV, DeVore R, Kerr RN, Crawford J, Natale RR, Dunphy F, Kalman L, Miller V, Lee JS, Moore M, et al: Randomized phase III trial of docetaxel versus vinorelbine or ifosfamide in patients with advanced non-small-cell lung cancer previously treated with platinum-containing chemotherapy regimens. The TAX 320 Non-Small cell lung cancer study group. J Clin Oncol. 18:2354–2362. 2000.PubMed/NCBI
12	Hanna N, Shepherd FA, Fossella FV, Pereira JR, De Marinis F, von Pawel J, Gatzemeier U, Tsao TC, Pless M, Muller T, et al: Randomized phase 111 trial of pemetrexed versus doeetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy. J Clin Onco1. 22:1589–1597. 2004. View Article : Google Scholar
13	Shepherd FA, Pereira J Rodrigues, Ciuleanu T, Tan EH, Hirsh V, Thongprasert S, Campos D, Maoleekoonpiroj S, Smylie M, Martins R, et al: Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med. 353:123–132. 2005. View Article : Google Scholar : PubMed/NCBI
14	Di Maio M, Perrone F, Chiodini P, Gallo C, Camps C, Schuette W, Quoix E, Tsai CM and Gridelli C: Individual patient data meta-analysis of docetaxel administered once every3 weeks compared with once every week second-line treatment of advanced non-small-cell lung cancer. J Clin Oncol. 25:1377–1382. 2007. View Article : Google Scholar : PubMed/NCBI
15	Peterson P, Park K, Fossella F, Gatzemeier U, John W and Scagliotti GV: Is pemetrexed more effective in adenocarcinoma and large cell lung cancer than in squamous cell carcinoma? A retrospective analysis of a phase III trial of pemetrexed vs docetaxel in previously treated patients with advanced non-small cell lung cancer (NSCLC). J Thorac Oncol. 2:(Suppl 4). s8512007. View Article : Google Scholar
16	Scagliotti GV, Parikh P, von Pawel J, Biesma B, Vansteenkiste J, Manegold C, Serwatowski P, Gatzemeier U, Digumarti R, Zukin M, et al: Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol. 26:3543–3551. 2008. View Article : Google Scholar : PubMed/NCBI
17	Scagliotti G, Hanna N, Fossella F, Sugarman K, Blatter J, Peterson P, Simms L and Shepherd FA: The differential efficacy of pemetrexed according to NSCLC histology: A review of two phase III studies. Oncologist. 14:253–263. 2009. View Article : Google Scholar : PubMed/NCBI
18	Zhang QC, Jiang SJ, Zhang S and Ma XB: Histone deacetylase inhibitor trichostatin A enhances antitumor effects of docetaxel or erlotinib in A549 cell line. Asian Pac J Cancer Prev. 13:3471–3476. 2012. View Article : Google Scholar : PubMed/NCBI
19	Wu DM, Zhang P, Xu GC, Tong AP, Zhou C, Lang JY and Wang CT: Pemetrexed induces G1 phase arrest and apoptosis through inhibiting Akt activation in human non small lung cancer cell line A549. Asian Pac J Cancer Prev. 16:1507–1513. 2015. View Article : Google Scholar : PubMed/NCBI
20	Tsai MS, Weng SH, Chen HJ, Chiu YF, Huang YC, Tseng SC, Kuo YH and Lin YW: Inhibition of p38 MAPK-dependent excision repair cross-complementing 1 expression decreases the DNA repair capacity to sensitize lung cancer cells to etoposide. Mol Cancer Ther. 11:561–571. 2012. View Article : Google Scholar : PubMed/NCBI
21	Liu YP, Ling Y, Qi QF, Zhang YP, Zhang CS, Zhu CT, Wang MH and Pan YD: The effects of ERCC1 expression levels on the chemosensitivity of gastric cancer cells to platinum agents and survival in gastric cancer patients treated with oxaliplatin-based adjuvant chemotherapy. Oncol Lett. 5:935–942. 2013.PubMed/NCBI
22	Cai Y, Yan X, Zhang G, Zhao W and Jiao S: The predictive value of ERCC1 and p53 for the effect of panobinostat and cisplatin combination treatment in NSCLC. Oncotarget. 6:18997–19005. 2015. View Article : Google Scholar : PubMed/NCBI
23	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
24	Fleeman N, Bagust A, McLeod C, Greenhalgh J, Boland A, Dundar Y, Dickson R, Smith C Tudur, Davis H, Green J and Pearson M: Pemetrexed for the first-line treatment of locally advanced or metastatic non-small cell lung cancer. Health Technol Assess. 14:(Suppl 1). S47–S53. 2010. View Article : Google Scholar
25	Pereira JR, Cheng R, Orlando M, Kim JH and Barraclough H: Elderly subset analysis of randomized phase III study comparing pemetrexed plus carboplatin with docetaxel plus carboplatin as first-line treatment for patients with locally advanced or metastatic non-small cell lung cancer. Drugs R D. 13:289–296. 2013. View Article : Google Scholar : PubMed/NCBI