Limits...
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

PAK4 knockdown inhibits the cisplatin resistance in cervical cancer cells. a: PAK4 mRNA level in Hela cells which were transfected with the PAK4-targeted siRNA (siRNA-PAK4) or with the control siRNA (siRNA-Con) with a concentration of 25 or 50 nM; b: Western blot analysis of PAK4 in protein level in the siRNA-PAK4- or siRNA-Con-transfected Hela cells; C and D: Influence of the transfection with siRNA-PAK4 or with siRNA-Con on the viability of Hela (c) and CaSki (d) cells, post the treatment with5 μM (for Hela cells) or 10 μM (for CaSki cells) cisplatin for 12, 24 or 48 h. Each value was averaged for triple independent results. *P < 0.05, **P < 0.01 or ***P < 0.001, ns: no significance
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4584462&req=5

Fig3: PAK4 knockdown inhibits the cisplatin resistance in cervical cancer cells. a: PAK4 mRNA level in Hela cells which were transfected with the PAK4-targeted siRNA (siRNA-PAK4) or with the control siRNA (siRNA-Con) with a concentration of 25 or 50 nM; b: Western blot analysis of PAK4 in protein level in the siRNA-PAK4- or siRNA-Con-transfected Hela cells; C and D: Influence of the transfection with siRNA-PAK4 or with siRNA-Con on the viability of Hela (c) and CaSki (d) cells, post the treatment with5 μM (for Hela cells) or 10 μM (for CaSki cells) cisplatin for 12, 24 or 48 h. Each value was averaged for triple independent results. *P < 0.05, **P < 0.01 or ***P < 0.001, ns: no significance

Mentions: To further confirm the effect of PAK4 on cisplatin efficacy, we knockdown the PAK4 expression, and re-evaluated the cisplatin-mediated viability reduction in both Hela and Caski cells. Results indicated that PAK4 was significantly downregulated in both mRNA (p < 0.01 for 25 or 50 nM, Fig. 3a) and protein levels (p < 0.001 for 25 or 50 nM, Fig. 3b). And then we also re-examined the cisplatin-mediated viability reduction in both types of cells. It was demonstrated in Fig. 3c that the transfection with 50 nM siRNA-PAK4 significantly aggravated the cisplatin-mediated viability reduction at either 24 or 48 h post treatment (p < 0.05 or p < 0.01). And Fig. 3d also indicated that the siRNA-PAK4 transfection markedly deteriorated the cisplatin-mediated viability reduction at either 24 or 48 h post treatment (p < 0.05 respectively). Therefore, the PAK4 knockdown sensitized Hela and Caski cells to cisplatin.Fig. 3


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)

PAK4 knockdown inhibits the cisplatin resistance in cervical cancer cells. a: PAK4 mRNA level in Hela cells which were transfected with the PAK4-targeted siRNA (siRNA-PAK4) or with the control siRNA (siRNA-Con) with a concentration of 25 or 50 nM; b: Western blot analysis of PAK4 in protein level in the siRNA-PAK4- or siRNA-Con-transfected Hela cells; C and D: Influence of the transfection with siRNA-PAK4 or with siRNA-Con on the viability of Hela (c) and CaSki (d) cells, post the treatment with5 μM (for Hela cells) or 10 μM (for CaSki cells) cisplatin for 12, 24 or 48 h. Each value was averaged for triple independent results. *P < 0.05, **P < 0.01 or ***P < 0.001, ns: no significance
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4584462&req=5

Fig3: PAK4 knockdown inhibits the cisplatin resistance in cervical cancer cells. a: PAK4 mRNA level in Hela cells which were transfected with the PAK4-targeted siRNA (siRNA-PAK4) or with the control siRNA (siRNA-Con) with a concentration of 25 or 50 nM; b: Western blot analysis of PAK4 in protein level in the siRNA-PAK4- or siRNA-Con-transfected Hela cells; C and D: Influence of the transfection with siRNA-PAK4 or with siRNA-Con on the viability of Hela (c) and CaSki (d) cells, post the treatment with5 μM (for Hela cells) or 10 μM (for CaSki cells) cisplatin for 12, 24 or 48 h. Each value was averaged for triple independent results. *P < 0.05, **P < 0.01 or ***P < 0.001, ns: no significance
Mentions: To further confirm the effect of PAK4 on cisplatin efficacy, we knockdown the PAK4 expression, and re-evaluated the cisplatin-mediated viability reduction in both Hela and Caski cells. Results indicated that PAK4 was significantly downregulated in both mRNA (p < 0.01 for 25 or 50 nM, Fig. 3a) and protein levels (p < 0.001 for 25 or 50 nM, Fig. 3b). And then we also re-examined the cisplatin-mediated viability reduction in both types of cells. It was demonstrated in Fig. 3c that the transfection with 50 nM siRNA-PAK4 significantly aggravated the cisplatin-mediated viability reduction at either 24 or 48 h post treatment (p < 0.05 or p < 0.01). And Fig. 3d also indicated that the siRNA-PAK4 transfection markedly deteriorated the cisplatin-mediated viability reduction at either 24 or 48 h post treatment (p < 0.05 respectively). Therefore, the PAK4 knockdown sensitized Hela and Caski cells to cisplatin.Fig. 3

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