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PAK4 confers the malignance of cervical cancers and contributes to the cisplatin-resistance in cervical cancer cells via PI3K/AKT pathway.

Shu XR, Wu J, Sun H, Chi LQ, Wang JH - Diagn Pathol (2015)

Bottom Line: In addition, the PI3K/Akt pathway has been implicated in the PAK4-confered cisplatin resistance.And the PI3K/Akt inhibitor, LY294002, markedly deteriorated the cisplatin-mediated viability reduction of Hela or Caski cells, indicating the involvement of PI3K/Akt pathway in the cisplatin resistance in cervical cancer cells.This study has confirmed the significant prognostic role of PAK4 level in cervical cancer patients and has recognized the regulatory role in cervical cancer progression.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmaceutical Science and Technology, Tianjin University, No. 92, Weijin Road, Nankai District, Tianjin, 300072, China.

ABSTRACT

Background: Multiple protein or microRNA markers have been recognized to contribute to the progression and recurrence of cervical cancers. Particular those, which are associated with the chemo- or radio-resistance of cervical cancers, have been proposed to be promising and to facilitate the definition for cervical cancer treatment options.

Methods: This study was designed to explore the potential prognosis value of p21-activated kinase (PAK)-4 in cervical cancer, via the Kaplan-Meier analysis, log-rank test and Cox regression analysis, and then to investigate the regulatory role of PAK4 in the cisplatin resistance in cervical cancer cells, via the strategies of both PAK4 overexpression and PAK4 knockout.

Results: It was demonstrated that PAK4 was upregulated in cervical cancer tissues, in an association with the cancer's malignance variables such as FIGO stage, lymph node or distant metastasis and the poor histological grade. The high PAK4 expression was also independently associated with poor prognosis to cervical cancer patients. Moreover, PAK4 confers cisplatin resistance in cervical cancer Hela or Caski cells. In addition, the PI3K/Akt pathway has been implicated in the PAK4-confered cisplatin resistance. And the PI3K/Akt inhibitor, LY294002, markedly deteriorated the cisplatin-mediated viability reduction of Hela or Caski cells, indicating the involvement of PI3K/Akt pathway in the cisplatin resistance in cervical cancer cells.

Conclusion: This study has confirmed the significant prognostic role of PAK4 level in cervical cancer patients and has recognized the regulatory role in cervical cancer progression. Moreover, our study has indicated that PAK4 also confers the chemoresistance of cervical cancer cells in a PI3K/Akt-dependent way. Thus, our study indicates PAK4 as a promising marker for cervical cancer treatment.

No MeSH data available.


Related in: MedlinePlus

Overexpressed PAK4 ameliorates the cisplatin-induced viability reduction of cervical cancer cells.a and b: The percent viability of Hela (a) and CaSki (b) cells which were transfected with control pcDNA3.1 (pcDNA3.1-Con) or pcDNA3.1-PAK4, with or without the treatment with 5 μM (for Hela cells) or 10 μM (for CaSki cells) cisplatin for 24 h; c and d: Time-dependence of the influence of the transfection with pcDNA3.1-Con or with pcDNA3.1-PAK4 on the viability of Hela (c) and CaSki (d) cells, in the presence of 5 μM (for Hela cells) or 10 μM (for CaSki cells) cisplatin. All results were averaged for triple independent experiments. *P < 0.05, **P < 0.01 or ns: no significance
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Fig2: Overexpressed PAK4 ameliorates the cisplatin-induced viability reduction of cervical cancer cells.a and b: The percent viability of Hela (a) and CaSki (b) cells which were transfected with control pcDNA3.1 (pcDNA3.1-Con) or pcDNA3.1-PAK4, with or without the treatment with 5 μM (for Hela cells) or 10 μM (for CaSki cells) cisplatin for 24 h; c and d: Time-dependence of the influence of the transfection with pcDNA3.1-Con or with pcDNA3.1-PAK4 on the viability of Hela (c) and CaSki (d) cells, in the presence of 5 μM (for Hela cells) or 10 μM (for CaSki cells) cisplatin. All results were averaged for triple independent experiments. *P < 0.05, **P < 0.01 or ns: no significance

Mentions: To further investigate the association of PAK4 with the poor prognosis of cervical cancer patients, we examined the influence of PAK4 overexpression on the sensitivity of Hela and Caski cells to cisplatin. It was indicated in Fig. 2a that the PAK4 overexpression posed no obvious influence on the viability of Hela cells, compared to the control plasmid and the blank control. However, the cellular viability decreased dramatically post the 5 μM cisplatin treatment (Column 4 vs Column 1, p < 0.01). Moreover, the transfection with pcDNA3.1-PAK4 markedly ameliorated the viability reduction by the cisplatin treatment, compared to the transfection with the pcDNA3.1-Con plasmid (Column 6 vs Column 5, p < 0.01), whereas there was no significant difference between the pcDNA3.1-Con-transfected and blank Hela cells (Column 5 vs Column 4). Then we re-examined such influence of PAK4 overexpression in Caski cells, and results demonstrated that the viability of the pcDNA3.1-PAK4-transfected Caski cells was also significantly higher than the pcDNA3.1-Con-transfected or the blank Caski cells (p < 0.05, Column 6 vs Column 5, Fig. 2b). In addition, we examined the time-dependence of the cellular viability amelioration by PAK4 overexpression in the two types of cells. It was indicated that such amelioration was significant at 24 or 48 h post the transfection in both Hela (p < 0.05 or p < 0.01, Fig. 2c) and Caski (either p < 0.01, Fig. 2d) cells. Therefore, PAK4 inhibited the sensitivity of Hela and Caski cells to cisplatin.Fig. 2


PAK4 confers the malignance of cervical cancers and contributes to the cisplatin-resistance in cervical cancer cells via PI3K/AKT pathway.

Shu XR, Wu J, Sun H, Chi LQ, Wang JH - Diagn Pathol (2015)

Overexpressed PAK4 ameliorates the cisplatin-induced viability reduction of cervical cancer cells.a and b: The percent viability of Hela (a) and CaSki (b) cells which were transfected with control pcDNA3.1 (pcDNA3.1-Con) or pcDNA3.1-PAK4, with or without the treatment with 5 μM (for Hela cells) or 10 μM (for CaSki cells) cisplatin for 24 h; c and d: Time-dependence of the influence of the transfection with pcDNA3.1-Con or with pcDNA3.1-PAK4 on the viability of Hela (c) and CaSki (d) cells, in the presence of 5 μM (for Hela cells) or 10 μM (for CaSki cells) cisplatin. All results were averaged for triple independent experiments. *P < 0.05, **P < 0.01 or ns: no significance
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Fig2: Overexpressed PAK4 ameliorates the cisplatin-induced viability reduction of cervical cancer cells.a and b: The percent viability of Hela (a) and CaSki (b) cells which were transfected with control pcDNA3.1 (pcDNA3.1-Con) or pcDNA3.1-PAK4, with or without the treatment with 5 μM (for Hela cells) or 10 μM (for CaSki cells) cisplatin for 24 h; c and d: Time-dependence of the influence of the transfection with pcDNA3.1-Con or with pcDNA3.1-PAK4 on the viability of Hela (c) and CaSki (d) cells, in the presence of 5 μM (for Hela cells) or 10 μM (for CaSki cells) cisplatin. All results were averaged for triple independent experiments. *P < 0.05, **P < 0.01 or ns: no significance
Mentions: To further investigate the association of PAK4 with the poor prognosis of cervical cancer patients, we examined the influence of PAK4 overexpression on the sensitivity of Hela and Caski cells to cisplatin. It was indicated in Fig. 2a that the PAK4 overexpression posed no obvious influence on the viability of Hela cells, compared to the control plasmid and the blank control. However, the cellular viability decreased dramatically post the 5 μM cisplatin treatment (Column 4 vs Column 1, p < 0.01). Moreover, the transfection with pcDNA3.1-PAK4 markedly ameliorated the viability reduction by the cisplatin treatment, compared to the transfection with the pcDNA3.1-Con plasmid (Column 6 vs Column 5, p < 0.01), whereas there was no significant difference between the pcDNA3.1-Con-transfected and blank Hela cells (Column 5 vs Column 4). Then we re-examined such influence of PAK4 overexpression in Caski cells, and results demonstrated that the viability of the pcDNA3.1-PAK4-transfected Caski cells was also significantly higher than the pcDNA3.1-Con-transfected or the blank Caski cells (p < 0.05, Column 6 vs Column 5, Fig. 2b). In addition, we examined the time-dependence of the cellular viability amelioration by PAK4 overexpression in the two types of cells. It was indicated that such amelioration was significant at 24 or 48 h post the transfection in both Hela (p < 0.05 or p < 0.01, Fig. 2c) and Caski (either p < 0.01, Fig. 2d) cells. Therefore, PAK4 inhibited the sensitivity of Hela and Caski cells to cisplatin.Fig. 2

Bottom Line: In addition, the PI3K/Akt pathway has been implicated in the PAK4-confered cisplatin resistance.And the PI3K/Akt inhibitor, LY294002, markedly deteriorated the cisplatin-mediated viability reduction of Hela or Caski cells, indicating the involvement of PI3K/Akt pathway in the cisplatin resistance in cervical cancer cells.This study has confirmed the significant prognostic role of PAK4 level in cervical cancer patients and has recognized the regulatory role in cervical cancer progression.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmaceutical Science and Technology, Tianjin University, No. 92, Weijin Road, Nankai District, Tianjin, 300072, China.

ABSTRACT

Background: Multiple protein or microRNA markers have been recognized to contribute to the progression and recurrence of cervical cancers. Particular those, which are associated with the chemo- or radio-resistance of cervical cancers, have been proposed to be promising and to facilitate the definition for cervical cancer treatment options.

Methods: This study was designed to explore the potential prognosis value of p21-activated kinase (PAK)-4 in cervical cancer, via the Kaplan-Meier analysis, log-rank test and Cox regression analysis, and then to investigate the regulatory role of PAK4 in the cisplatin resistance in cervical cancer cells, via the strategies of both PAK4 overexpression and PAK4 knockout.

Results: It was demonstrated that PAK4 was upregulated in cervical cancer tissues, in an association with the cancer's malignance variables such as FIGO stage, lymph node or distant metastasis and the poor histological grade. The high PAK4 expression was also independently associated with poor prognosis to cervical cancer patients. Moreover, PAK4 confers cisplatin resistance in cervical cancer Hela or Caski cells. In addition, the PI3K/Akt pathway has been implicated in the PAK4-confered cisplatin resistance. And the PI3K/Akt inhibitor, LY294002, markedly deteriorated the cisplatin-mediated viability reduction of Hela or Caski cells, indicating the involvement of PI3K/Akt pathway in the cisplatin resistance in cervical cancer cells.

Conclusion: This study has confirmed the significant prognostic role of PAK4 level in cervical cancer patients and has recognized the regulatory role in cervical cancer progression. Moreover, our study has indicated that PAK4 also confers the chemoresistance of cervical cancer cells in a PI3K/Akt-dependent way. Thus, our study indicates PAK4 as a promising marker for cervical cancer treatment.

No MeSH data available.


Related in: MedlinePlus