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Updated: Apr 28, 2026

Cytotoxic Efficacy of Photodynamic Therapy in Osteosarcoma Cells In Vitro
Published on: March 18, 2014
Autophagy in osteosarcoma
Janice Santiago O'Farrill1, Nancy Gordon
1Department of Pediatrics-Research, The Children's Cancer Hospital, University of Texas M.D. Anderson Cancer Center, Houston, TX, 77030, USA.
Abstract:
Osteosarcoma (OS) metastatic disease is resistant to conventional chemotherapy. Tumor resistance to chemotherapy has been one of the major areas of concern to clinicians and the topic of many laboratory investigators. Evaluation of mechanisms implicated in OS lung metastasis resistance to chemotherapy has been the focus of some of our most recent work. We have previously demonstrated the therapeutic efficacy of aerosol gemcitabine (GCB) in OS lung metastases. However, a subset of cells fails to respond to GCB treatment and persists as isolated lung metastases in vivo. Autophagy, a physiological mechanism that supports nutritional deprivation under stressful conditions, has been implicated in tumor resistance to chemotherapy. We demonstrated the induction of autophagy by GCB in LM7 metastatic human OS cells and K7M3 metastatic murine OS cells. Inhibition of autophagy resulted in increased sensitivity to GCB in LM7 cells. By contrast, inhibiting autophagy in K7M3 cells decreased GCB sensitivity. Defining the role autophagy plays in chemotherapy response in different tumor types has become of greater importance in order to identify the best suitable therapeutic approach. In this chapter, we summarize some of the most recent work related to autophagy in OS, identify some of the known mechanisms, and address the different roles autophagy plays in chemotherapy response.
Insights
Autophagy influences chemotherapy resistance in osteosarcoma lung metastases. Inhibiting autophagy increased gemcitabine sensitivity in human cells but decreased it in mouse cells, highlighting varied roles.
Area of Science:
- Oncology
- Cell Biology
- Pharmacology
Background:
- Osteosarcoma (OS) lung metastasis exhibits resistance to conventional chemotherapy, posing a significant clinical challenge.
- Autophagy, a cellular self-degradation process, is implicated in tumor resistance to various chemotherapeutic agents.
- Previous work demonstrated aerosol gemcitabine (GCB) efficacy in OS lung metastases, yet a subset of cells remains unresponsive.
Purpose of the Study:
- To investigate the role of autophagy in chemotherapy resistance in osteosarcoma lung metastases.
- To evaluate the impact of autophagy modulation on gemcitabine (GCB) sensitivity in different osteosarcoma cell lines.
Main Methods:
- Assessment of autophagy induction by GCB in human (LM7) and murine (K7M3) metastatic OS cells.
- Evaluation of GCB sensitivity following autophagy inhibition in both cell lines.
- Analysis of in vivo therapeutic efficacy of GCB in OS lung metastases.
Main Results:
- GCB treatment induced autophagy in both LM7 and K7M3 osteosarcoma cells.
- Inhibition of autophagy enhanced GCB sensitivity in LM7 human cells.
- Conversely, autophagy inhibition decreased GCB sensitivity in K7M3 murine cells.
Conclusions:
- Autophagy plays a differential role in mediating chemotherapy response in osteosarcoma lung metastases.
- Understanding these varied roles is crucial for developing targeted therapeutic strategies against OS metastasis.
- Further research is needed to define optimal approaches for modulating autophagy in cancer therapy.
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