c-Met antisense oligodeoxynucleotides increase sensitivity of human glioma cells to paclitaxel

Sheng-Hua Chu1, Yan-Bin Ma, Dong-Fu Feng

  • 1Department of Neurosurgery, No.3 People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 201900, PR China. shenghuachu@126.com

Oncology Reports
|June 2, 2010
PubMed

Insights

Antisense c-Met oligodeoxynucleotides enhance human glioma cell sensitivity to paclitaxel. Combining these agents offers a promising strategy for treating human glioma, inhibiting growth and inducing apoptosis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Glioblastoma is an aggressive brain tumor with limited treatment options.
  • Paclitaxel is a chemotherapy drug used in cancer treatment.
  • The c-Met signaling pathway is implicated in glioma progression and drug resistance.

Purpose of the Study:

  • To investigate if antisense c-Met oligodeoxynucleotides can sensitize human glioma cells to paclitaxel.
  • To evaluate the combined effect of paclitaxel and c-Met antisense oligodeoxynucleotides on glioma cell growth and apoptosis.

Main Methods:

  • Cell culture techniques were employed to grow human glioma cell lines (U251 and SHG44).
  • Antisense c-Met oligodeoxynucleotides were synthesized and applied to glioma cells.
  • Flow cytometry and tissue chemistry analyses were performed to assess cell viability, apoptosis, and protein expression.
  • Statistical analysis (P<0.01) was used to determine significance.

Main Results:

  • The combination of paclitaxel and c-Met antisense oligodeoxynucleotides significantly inhibited human glioma cell growth compared to single agents.
  • Combined treatment induced apoptosis in U251 and SHG44 cells more effectively than paclitaxel or oligodeoxynucleotides alone.
  • c-Met protein expression was induced by the combined therapy, suggesting pathway modulation.

Conclusions:

  • Antisense c-Met oligodeoxynucleotides significantly enhance the sensitivity of human glioma cells to paclitaxel.
  • The combined administration of paclitaxel and c-Met antisense oligodeoxynucleotides represents a novel and potentially effective therapeutic strategy for human glioma.

Related Concept Videos

Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
Drugs that Stabilize Microtubules01:15

Drugs that Stabilize Microtubules

Microtubules are dynamic structures that undergo cycles of catastrophe and rescue. The microtubules play a central role in cell division by forming the spindle apparatus for segregating the chromosomes. This makes them ideal targets for regulating dividing cells in tumors and malignant cancer cells. Microtubule stabilizing drugs help stabilize the microtubule formation and promote its polymerization. Paclitaxel was the first microtubule stabilizing agent used as anticancer drug in chemotherapy...
Treatment Resistent Cancers02:56

Treatment Resistent Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...