J Lung Cancer.  2009 Jun;8(1):21-30. 10.6058/jlc.2009.8.1.21.

Investigating Effective Combinations of Anti-cancer Drugs and Radiation Therapy for Treating Non-small Cell Lung Cancer with Using Two Cell Lines

• Oh IJ
• Cho HJ
• Manaljav T
• Kwon YS
• Kim KS
• Lim SC
• Kim YC
• Ahn SJ

• KMID: 1464706
• DOI: http://doi.org/10.6058/jlc.2009.8.1.21

Abstract

PURPOSE: Radiotherapy had been used for treating unresectable locally advanced non-small cell lung cancer (NSCLC). However, the survival rate after radiotherapy alone is low and this primarily due to the failure of local disease control and distant metastasis. For achieving better disease control, radiotherapy has recently been combined with chemotherapy in various ways. In this study, we aimed to find the most effective combination of chemotherapy and radiotherapy for treating NSCLC.
MATERIALS AND METHODS
Two human lung cancer cell lines (NCI-H520 and A549) and various chemotherapeutic agents (paclitaxel, docetaxel, gemcitabine and cisplatin) were used for this study. The radiation doses were 0, 2, 4 and 8 Gy. After processing various combinations according to the radiation doses and the concentrations of thechemotherapeutic agents, cell survival was quantified by MTT (3-(4,5-Dimethylhiazol- 2-yl)-2,5-diphenyltetrazoliumbromide) assay. For the evaluation of synergism between chemotherapy and radiotherapy, we used a combination index that as calculated by Chou and Talalay's method and with using Calcusyn software.
RESULTS
Among the various combinations of chemotherapeutic agents and radiation doses, concurrent chemoradiation therapy (CCRT) led to the highest apoptosis rate and it showed frequent synergism. When taxane was administrated as a chemotherapeutic agent, chemotherapy followed by radiotherapy was the most effective combination. When high-dose chemotherapeutic agents were added to CCRT, induction chemotherapy resulted in a higher apoptosis rate and more frequent synergism than did consolidation chemotherapy.
CONCLUSION
When radiotherapy is combined with chemotherapy for treating the NCI-H520 and A549 cell lines, CCRT is the most effective combination. If a high-dose chemotherapeutic agent is added to CCRT, then induction chemotherapy is more effective than consolidation chemotherapy.

Keyword

Non-small cell lung carcinoma; Concurrent chemoradiation; Induction chemotherapy I

MeSH Terms

Apoptosis
Bridged Compounds
Carcinoma, Non-Small-Cell Lung
Cell Line
Cell Survival
Consolidation Chemotherapy
Deoxycytidine
Humans
Induction Chemotherapy
Lung Neoplasms
Neoplasm Metastasis
Survival Rate
Taxoids
Bridged Compounds
Deoxycytidine
Taxoids

Figure

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  Fig. 1. Schematic diagram of the experimental designs in this study. After the indicated treatment, the cells were processed for clonogenic survival using a MTT assay. Chemo: chemotherapy, Rad: radiation, iChemo: induction chemotherapy, cChemo: consolidation chemotherapy, MTT: 3-(4,5-Dimethyl-thiazol-2-yl)-2,5-diphenyltetrazoliu mbromide.

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  Fig. 2. Sequence-dependent antiproliferative effects at various concentrations of chemotherapeutic agents in the NCI-H520 cell line. The cell viabilities are shown on (A) paclitaxel 25 nM, (B) docetaxel 25 ng/mL, (C) gemcitabine 100 ng/mL, and (D) cisplatin 5 g/mL, respectively. *synergism (CI values of 0.7 to 0.3), † strong synergism (CI values less than 0.3).

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  Fig. 3. Sequence-dependent antiproliferative effects according to the various concentrations of chemotherapeutic agents in the A549 cell line. The cell viability is shown on (A) paclitaxel 10 nM, (B) docetaxel 5 ng/mL, (C) gemcitabine 2.5 ng/mL, and (D) cisplatin 2.5 g/mL, respectively. *synergism (CI values of 0.7 to 0.3), † strong synergism (CI values less than 0.3).

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  Fig. 4. Flow cytometry analysis of the cell cycle on the A549 cell line. Among (A) only gemcitabine 2.5 ng/mL, (B) radiation 4 Gy followed by gemcitabine 2.5 ng/mL, (C) gemcitabine 2.5 ng/mL followed by radiation, and (D) CCRT with gemcitabine, the greatest apoptotic peak is shown in CCRT. M1: sub G1-phase, M2: G1-phase, M3: S-phase, M4: G2/M-phase.

Reference

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