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Improved Response to nab-Paclitaxel Compared with Cremophor-Solubilized Paclitaxel is Independent of Secreted Protein Acidic and Rich in Cysteine Expression.

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Presentation on theme: "Improved Response to nab-Paclitaxel Compared with Cremophor-Solubilized Paclitaxel is Independent of Secreted Protein Acidic and Rich in Cysteine Expression."— Presentation transcript:

1 Improved Response to nab-Paclitaxel Compared with Cremophor-Solubilized Paclitaxel is Independent of Secreted Protein Acidic and Rich in Cysteine Expression in Non-Small Cell Lung Cancer  Huanjie Shao, PhD, Haikuo Tang, MD, PhD, Oreste E. Salavaggione, MD, Chunrong Yu, PhD, Bonnie Hylander, PhD, Wei Tan, MA, Elizabeth Repasky, PhD, Alex A. Adjei, MD, PhD, Grace K. Dy, MD  Journal of Thoracic Oncology  Volume 6, Issue 6, Pages (June 2011) DOI: /JTO.0b013e318217b739 Copyright © 2011 International Association for the Study of Lung Cancer Terms and Conditions

2 FIGURE 1 Representative examples of methylation-specific PCR assay for SPARC in NSCLC cell lines and NSCLC xenografts. H460 cells were treated with DEC (5 μM) in vitro for 3 days. PCR products were visualized on 1.5% agarose gels. w/, treated with; Me, methylated; UM, unmethylated; PCR, polymerase chain reaction; SPARC, secreted protein acidic and rich in cysteine; NSCLC, non-small cell lung cancer; DEC, 5-Aza-2′-deoxycytidine. Journal of Thoracic Oncology 2011 6, DOI: ( /JTO.0b013e318217b739) Copyright © 2011 International Association for the Study of Lung Cancer Terms and Conditions

3 FIGURE 2 Western blot showing that SPARC expression in xenografts and NSCLC cell lines is up-regulated on treatment with DEC. A, NSCLC cell lines A549, H460, and H157 were treated with 5 μM DEC for 3 days in vitro and then harvested for RT-PCR. B, PD NSCLC xenografts and H460 xenografts treated with or without DEC 1.5 mg/kg/d, and xenografts were harvested for SPARC expression analysis. GAPDH were used as the endogenous control. w/, treated with; SPARC, secreted protein acidic and rich in cysteine; PD NSCLC, patient-derived non-small cell lung cancer; DEC, 5-Aza-2′-deoxycytidine; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; RT-PCR, real-time polymerase chain reaction. Journal of Thoracic Oncology 2011 6, DOI: ( /JTO.0b013e318217b739) Copyright © 2011 International Association for the Study of Lung Cancer Terms and Conditions

4 FIGURE 3 Efficacy of ABX compared with taxol in PD NSCLC xenografts. SCID mice bearing SPARC-positive xenografts (NSCLC_16372) (A), SPARC-intermediate xenografts (NSCLC_15946) (B), or SPARC-negative xenografts, NSCLC_16465 (C) and NSCLC_16591 (D), were treated with vehicle, equitoxic dose of taxol (13.4 mg/kg), or ABX (30 mg/kg). The overall antitumor efficacy of drugs was measured as tumor volumes every 2 to 3 days. The error bars represented the standard error of the mean. PD NSCLC, patient-derived non-small cell lung cancer; SCID, severe combined immunodeficiency; SPARC, secreted protein acidic and rich in cysteine. Journal of Thoracic Oncology 2011 6, DOI: ( /JTO.0b013e318217b739) Copyright © 2011 International Association for the Study of Lung Cancer Terms and Conditions

5 FIGURE 4 Enhanced antitumor efficacy of taxol and ABX by pretreatment with DEC in SPARC-negative xenografts. A–C, SCID mice bearing SPARC-negative xenografts, NSCLC_16325 (A), NSCLC_16384 (B), or H460 (C), were administered with DEC (1.5 mg/kg), taxol (13.4 mg/kg) or ABX (30 mg/kg) alone or the combination of DEC and taxol or DEC and ABX. The overall antitumor efficacy of drugs was measured as tumor volumes every 2 to 3 days. The error bars represented the standard error of the mean. DEC, 5-Aza-2′-deoxycytidine; SPARC, secreted protein acidic and rich in cysteine; NSCLC, non-small cell lung cancer. Journal of Thoracic Oncology 2011 6, DOI: ( /JTO.0b013e318217b739) Copyright © 2011 International Association for the Study of Lung Cancer Terms and Conditions

6 FIGURE 5 Cell death rate analysis with NSCLC cell lines A549 and H460 in vitro showing additive antitumor activity of ABX or taxol by pretreatment with DEC. A and C, results of H460 cells treated with escalating concentrations of ABX or taxol after DEC 5μM pretreatment. B and D, results of A549 cells treated with escalating concentrations of ABX or taxol after DEC 5 μM pretreatment. Treated cells were harvested for cell death rates assay (*p < 0.05, compared with ABX or taxol treatment alone). Data represents mean ± standard deviation of three independent experiments. NSCLC, non-small cell lung cancer; DEC, 5-Aza-2′-deoxycytidine. Journal of Thoracic Oncology 2011 6, DOI: ( /JTO.0b013e318217b739) Copyright © 2011 International Association for the Study of Lung Cancer Terms and Conditions

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