Objective: Neoadjuvant chemotherapy (NAC) with paclitaxel (T) and cisplatin (P) was commonly used for the treatment of cervical cancer. However, little is known about the antineoplastic mechanism of NAC with TP in patient tissues in situ. In this study, we compared the proteomic profiles of cervical cancer in patients before and after NAC with TP to identify proteins that may shed light on the mechanism of TP action.
Methods: We collected cervical cancer tissues pre- and post-NAC with TP from 6 patients with local advanced cervical cancer and stored them at −80°C. Proteomes of 2 groups of cervical cancer tissues were analyzed by 2-dimensional gel electrophoresis and the differentially expressed proteins were identified by matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry. Some proteins that are differentially expressed were confirmed by Western blot.
Results: There were 13 proteins whose levels were significantly altered after NAC with TP. Compared with pre-NAC, 11 proteins were down-regulated, and 2 proteins were up-regulated in the post-NAC group. The down-regulated proteins were aldolase A, pyruvate kinase, enolase 1, heat shock protein 27 (HSP27), HSP70, actinin α1, lamin B1, eukaryotic translation elongation factor 1γ, annexin 1, epithelial cell marker protein1, keratin II-type. In contrast, apolipoprotein A1 and annexin V were up-regulated. The down-regulation of HSP27, HSP70, enolase 1, and aldolase A was verified by Western blot.
Conclusions: Differentially expressed proteins between cervical cancer tissues pre- and post-NAC with TP were identified by comparative proteomic approach. The NAC therapy with TP down-regulated proteins involved in energy production (glycolytic enzymes) and chaperones but up-regulated proteins involved in apoptosis. These findings shed new light on biomarkers associated with effect of chemotherapy.
- Cervical carcinoma
- Neoadjuvant chemotherapy
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The authors declare that there are no conflicts of interest.
This work was supported by the Changjiang Scholar fund (Y.Z.) and talent supporting fund from the Ministry of Education of China (NCET-07-0403) (B.Z.).