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Enhanced cytotoxic activity of cetuximab in EGFR-positive lung cancer by conjugating with gold nanoparticles.

Qian Y, Qiu M, Wu Q, Tian Y, Zhang Y, Gu N, Li S, Xu L, Yin R - Sci Rep (2014)

Bottom Line: Overall, the therapeutic effect of C225-AuNPs was more pronounced in EGFR(high) A549 cells compared with EGFR(low) H1299 cells.C225-AuNPs significantly suppressed A549 cell proliferation and migration capacity and accelerated apoptosis compared with C225, and this effect was probably due to enhanced EGFR endocytosis and the subsequent suppression of downstream signaling pathway.Finally in the tumor xenograft of nude mice, treatment with C225-AuNPs also led to a significant reduction in tumor weight and volume with low toxicity.

View Article: PubMed Central - PubMed

Affiliation: 1] Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, P.R. China 210009 [2] The First Clinical College, Nanjing Medical University, Nanjing, P.R. China 210029.

ABSTRACT
Cetuximab (C225) is a unique agent, targeting epidermal growth factor receptor (EGFR)-positive cancer. However, the therapeutic effect of C225 in EGFR high-expressing non-small cell lung cancer (NSCLC) remains poor. Here, we report that conjugation of C225 with gold nanoparticles (AuNPs) enhances the cytotoxicity of C225 in NSCLC both in vitro and in vivo. The NSCLC cell lines A549 (EGFR(high)) and H1299 (EGFR(low)) were employed to investigate different responses to C225, IgG-AuNPs and C225-AuNPs. The antitumor properties of C225-AuNPs were explored in vivo by establishing a tumor xenograft model in nude mice. Overall, the therapeutic effect of C225-AuNPs was more pronounced in EGFR(high) A549 cells compared with EGFR(low) H1299 cells. The cytotoxic effect of C225-AuNPs in A549 cells increased in a dose-dependent manner. C225-AuNPs significantly suppressed A549 cell proliferation and migration capacity and accelerated apoptosis compared with C225, and this effect was probably due to enhanced EGFR endocytosis and the subsequent suppression of downstream signaling pathway. Finally in the tumor xenograft of nude mice, treatment with C225-AuNPs also led to a significant reduction in tumor weight and volume with low toxicity. Our findings suggest that C225-AuNPs conjugate has promising potential for targeted therapy of EGFR positive NSCLC patients.

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Related in: MedlinePlus

Apoptotic evaluation of cell lines treated with indicated concentrations of C225, IgG-AuNPs or C225-AuNPs for 48 h using the FITC-Annexin V apoptosis Detection Kit I assay.A) A549 cells; B) H1299 cells. Values represent the means ± SD. (**p < 0.01; *p < 0.05).
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f4: Apoptotic evaluation of cell lines treated with indicated concentrations of C225, IgG-AuNPs or C225-AuNPs for 48 h using the FITC-Annexin V apoptosis Detection Kit I assay.A) A549 cells; B) H1299 cells. Values represent the means ± SD. (**p < 0.01; *p < 0.05).

Mentions: We next analyzed whether C225-AuNPs inhibited cell proliferation by inducing apoptosis. Treatment of A549 cells with C225-AuNPs (100 μg/mL) led to a significant increase in apoptosis compared with treatment of cells with C225 at the same concentration (40.2 ± 4.03% vs. 17.0 ± 2.67%, p < 0.01, Fig. 4A). In contrast, we observed no significant difference in the rate of apoptosis in H1299 cells following treatment with C225, IgG-AuNPs or C225-AuNPs at doses ranging between 1–100 mg/L (Fig. 4B). We also assessed the effect of these compounds on cell cycle. As shown in Fig. 5, treatment of A549 or H1299 cells with C225-AuNPs did not lead to a G1/G0 phase delay in either cell line compared with treatment with C225 and IgG-AuNPs. Taken together, these results suggest that C225-AuNPs induced cell apoptosis without altering cell cycle distribution.


Enhanced cytotoxic activity of cetuximab in EGFR-positive lung cancer by conjugating with gold nanoparticles.

Qian Y, Qiu M, Wu Q, Tian Y, Zhang Y, Gu N, Li S, Xu L, Yin R - Sci Rep (2014)

Apoptotic evaluation of cell lines treated with indicated concentrations of C225, IgG-AuNPs or C225-AuNPs for 48 h using the FITC-Annexin V apoptosis Detection Kit I assay.A) A549 cells; B) H1299 cells. Values represent the means ± SD. (**p < 0.01; *p < 0.05).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4265789&req=5

f4: Apoptotic evaluation of cell lines treated with indicated concentrations of C225, IgG-AuNPs or C225-AuNPs for 48 h using the FITC-Annexin V apoptosis Detection Kit I assay.A) A549 cells; B) H1299 cells. Values represent the means ± SD. (**p < 0.01; *p < 0.05).
Mentions: We next analyzed whether C225-AuNPs inhibited cell proliferation by inducing apoptosis. Treatment of A549 cells with C225-AuNPs (100 μg/mL) led to a significant increase in apoptosis compared with treatment of cells with C225 at the same concentration (40.2 ± 4.03% vs. 17.0 ± 2.67%, p < 0.01, Fig. 4A). In contrast, we observed no significant difference in the rate of apoptosis in H1299 cells following treatment with C225, IgG-AuNPs or C225-AuNPs at doses ranging between 1–100 mg/L (Fig. 4B). We also assessed the effect of these compounds on cell cycle. As shown in Fig. 5, treatment of A549 or H1299 cells with C225-AuNPs did not lead to a G1/G0 phase delay in either cell line compared with treatment with C225 and IgG-AuNPs. Taken together, these results suggest that C225-AuNPs induced cell apoptosis without altering cell cycle distribution.

Bottom Line: Overall, the therapeutic effect of C225-AuNPs was more pronounced in EGFR(high) A549 cells compared with EGFR(low) H1299 cells.C225-AuNPs significantly suppressed A549 cell proliferation and migration capacity and accelerated apoptosis compared with C225, and this effect was probably due to enhanced EGFR endocytosis and the subsequent suppression of downstream signaling pathway.Finally in the tumor xenograft of nude mice, treatment with C225-AuNPs also led to a significant reduction in tumor weight and volume with low toxicity.

View Article: PubMed Central - PubMed

Affiliation: 1] Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, P.R. China 210009 [2] The First Clinical College, Nanjing Medical University, Nanjing, P.R. China 210029.

ABSTRACT
Cetuximab (C225) is a unique agent, targeting epidermal growth factor receptor (EGFR)-positive cancer. However, the therapeutic effect of C225 in EGFR high-expressing non-small cell lung cancer (NSCLC) remains poor. Here, we report that conjugation of C225 with gold nanoparticles (AuNPs) enhances the cytotoxicity of C225 in NSCLC both in vitro and in vivo. The NSCLC cell lines A549 (EGFR(high)) and H1299 (EGFR(low)) were employed to investigate different responses to C225, IgG-AuNPs and C225-AuNPs. The antitumor properties of C225-AuNPs were explored in vivo by establishing a tumor xenograft model in nude mice. Overall, the therapeutic effect of C225-AuNPs was more pronounced in EGFR(high) A549 cells compared with EGFR(low) H1299 cells. The cytotoxic effect of C225-AuNPs in A549 cells increased in a dose-dependent manner. C225-AuNPs significantly suppressed A549 cell proliferation and migration capacity and accelerated apoptosis compared with C225, and this effect was probably due to enhanced EGFR endocytosis and the subsequent suppression of downstream signaling pathway. Finally in the tumor xenograft of nude mice, treatment with C225-AuNPs also led to a significant reduction in tumor weight and volume with low toxicity. Our findings suggest that C225-AuNPs conjugate has promising potential for targeted therapy of EGFR positive NSCLC patients.

Show MeSH
Related in: MedlinePlus