Improved therapeutic effectiveness by combining recombinant p14^ARF with antisense complementary DNA of EGFR in laryngeal squamous cell carcinoma

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• 作者：Feng Liu ; MD ; PhD^a ; ¹ ; JinTao Du ; PhD^a ; ¹ ; Junming Xian ; MD ; PhD^b ; ^{fxjming@163.com" class="auth_mail" title="E-mail the corresponding author} ; Yafeng Liu ; MM^a ; Shixi Liu ; MD ; PhD^a ; Yan Lin ; MD ; PhD^c
• 刊名：American Journal of Otolaryngology
• 出版年：2015
• 出版时间：November-December 2015
• 年：2015
• 卷：36
• 期：6
• 页码：763-771
• 全文大小：1069 K

文摘

The tumor suppressor p14^ARF and proto-oncogene epidermal growth factor receptor (EGFR) play important roles in the development of laryngeal squamous cell carcinoma (LSCC). This study was aimed to determine whether combining recombinant p14^ARF with antisense complementary DNA of EGFR could improve the therapeutic effectiveness in LSCC.

Materials and methods

After human larynx cancer cells (Hep-2) were infected with recombinant adenoviruses (Ad-p14^ARF and Ad-antisense EGFR) together or alone in vitro, the proliferation and cell cycle distribution of Hep-2 cells were detected by MTT assay and flow cytometer analysis, respectively. Furthermore, the antitumor effects of recombinant adenoviruses together or alone on Hep-2 xenografts were examined in vivo. The levels of p14^ARF and EGFR expressed in Hep-2 cells and xenografts were determined by western blot assay.

Results

Ad-p14^ARF combining with Ad-antisense EGFR markedly inhibited the Hep-2 proliferation compared with alone (P = 0.001, P = 0.002 respectively). Combination of Ad-p14^ARF and Ad-antisense EGFR led to the proportion of Hep-2 cells in G₀/G₁ phases increased by up to 86.9%. The down-expression of EGFR protein and overexpression of p14^ARF protein were observed in vitro and in vivo, and this effect was preserved when Ad-p14^ARF was combined with Ad-antisense EGFR. Besides, Ad-p14^ARF plus Ad-antisense EGFR significantly (P < 0.05) increased the antitumor activity against Hep-2 tumor xenografts comparing with Ad-p14^ARF or Ad-antisense EGFR alone.

Conclusion

Combination Ad-p14^ARF with Ad-antisense EGFR significantly increased the antitumor responses in LSCC. An effectively potential gene therapy to prevent proliferation of LSCC was provided.