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Effective inhibition of colon cancer cell growth with MgAl-layered double hydroxide (LDH) loaded 5-FU and PI3K/mTOR dual inhibitor BEZ-235 through apoptotic pathways

Journal Article


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Abstract


  • Colon cancer is the third most common cancer and the third largest cause of cancer-related death. Fluorouracil (5-FU) is the front-line chemotherapeutic agent for colon cancer. However, its response rate is less than 60%, even in combination with other chemotherapeutic agents. The side effects of 5-FU also limit its application. Nanoparticles have been used to deliver 5-FU, to increase its effectiveness and reduce side effects. Another common approach for colon cancer treatment is targeted therapy against the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway. A recently-invented inhibitor of this pathway, BEZ-235, has been tested in several clinical trials and has shown effectiveness and low side effects. Thus, it is a very promising drug for colon cancer treatment. The combination of these two drugs, especially nanoparticle-packed 5-FU and BEZ-235, has not been studied. In the present study, we demonstrated that nanoparticles of layered double hydroxide (LDH) loaded with 5-FU were more effective than a free drug at inhibiting colon cancer cell growth, and that a combination treatment with BEZ-235 further increased the sensitivity of colon cancer cells to the treatment of LDH-packed 5-FU (LDH-5-FU). BEZ-235 alone can decrease colon cancer HCT-116 cell viability to 46% of the control, and the addition of LDH-5-FU produced a greater effect, reducing cell survival to 8% of the control. Our data indicate that the combination therapy of nanodelivered 5-FU with a PI3K/Akt inhibitor, BEZ-235, may promise a more effective approach for colon cancer treatment.

Authors


  •   Li, Li (external author)
  •   Shao, Renfu (external author)
  •   Gu, Wenyi (external author)
  •   Xu, Zhi Ping (external author)
  •   Chen, Jiezhong

Publication Date


  • 2014

Citation


  • Chen, J., Shao, R., Li, L., Xu, Z. & Gu, W. (2014). Effective inhibition of colon cancer cell growth with MgAl-layered double hydroxide (LDH) loaded 5-FU and PI3K/mTOR dual inhibitor BEZ-235 through apoptotic pathways. International Journal of Nanomedicine, 9 (1), 3403-3411.

Scopus Eid


  • 2-s2.0-84904413870

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=1455&context=ihmri

Ro Metadata Url


  • http://ro.uow.edu.au/ihmri/438

Has Global Citation Frequency


Number Of Pages


  • 8

Start Page


  • 3403

End Page


  • 3411

Volume


  • 9

Issue


  • 1

Abstract


  • Colon cancer is the third most common cancer and the third largest cause of cancer-related death. Fluorouracil (5-FU) is the front-line chemotherapeutic agent for colon cancer. However, its response rate is less than 60%, even in combination with other chemotherapeutic agents. The side effects of 5-FU also limit its application. Nanoparticles have been used to deliver 5-FU, to increase its effectiveness and reduce side effects. Another common approach for colon cancer treatment is targeted therapy against the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway. A recently-invented inhibitor of this pathway, BEZ-235, has been tested in several clinical trials and has shown effectiveness and low side effects. Thus, it is a very promising drug for colon cancer treatment. The combination of these two drugs, especially nanoparticle-packed 5-FU and BEZ-235, has not been studied. In the present study, we demonstrated that nanoparticles of layered double hydroxide (LDH) loaded with 5-FU were more effective than a free drug at inhibiting colon cancer cell growth, and that a combination treatment with BEZ-235 further increased the sensitivity of colon cancer cells to the treatment of LDH-packed 5-FU (LDH-5-FU). BEZ-235 alone can decrease colon cancer HCT-116 cell viability to 46% of the control, and the addition of LDH-5-FU produced a greater effect, reducing cell survival to 8% of the control. Our data indicate that the combination therapy of nanodelivered 5-FU with a PI3K/Akt inhibitor, BEZ-235, may promise a more effective approach for colon cancer treatment.

Authors


  •   Li, Li (external author)
  •   Shao, Renfu (external author)
  •   Gu, Wenyi (external author)
  •   Xu, Zhi Ping (external author)
  •   Chen, Jiezhong

Publication Date


  • 2014

Citation


  • Chen, J., Shao, R., Li, L., Xu, Z. & Gu, W. (2014). Effective inhibition of colon cancer cell growth with MgAl-layered double hydroxide (LDH) loaded 5-FU and PI3K/mTOR dual inhibitor BEZ-235 through apoptotic pathways. International Journal of Nanomedicine, 9 (1), 3403-3411.

Scopus Eid


  • 2-s2.0-84904413870

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=1455&context=ihmri

Ro Metadata Url


  • http://ro.uow.edu.au/ihmri/438

Has Global Citation Frequency


Number Of Pages


  • 8

Start Page


  • 3403

End Page


  • 3411

Volume


  • 9

Issue


  • 1