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[A new photodynamic therapy drug toward gastric cancer MGC803 cell]
Jing-jing Chen1, Wu Wei, Ai-fang Ji
1Chinese Academy of Medical Sciences, Beijing, China.
Objective:
To investigate the treatment efficiency of a new photodynamic therapeutic(PDT) drug synthesized by our laboratory toward MGC803 cells and related mechanisms.
Methods:
Bleaching method was used to evaluate the photostability of drug upon repetitive illumination. MTT assay was used to determine the ability of new drug killing MGC803 cells after PDT. Laser scanning confocal microscopy (LSCM) was applied to investigate the subcellular localization of drug in MGC803 cells (mitochondria and/or lysosomes). Hoechst staining and flow cytometry(Annexin V/PI double-staining) were performed to detect the death mode of MGC803 cells after PDT.
Results:
This new PDT drug had good stability to light irradiation after repetitive illumination. MTT assay showed no cytotoxicity towards MGC803 cells only by drug or only by irradiation(P>0.05), but intense lethal effect was observed with drug and light combination(P<0.05). The phototoxicity of medicine increased with the elevation of concentration, the LD50 was 1.74 μmol/L, and reaching plateau at the concentration of 3.12 μmol/L, even increasing the concentration. LSCM found that drug localized in lysosomes of MGC803 cells. Hoechst staining showed that the death mode of cells was mainly necrosis and Annexin V/PI double-staining proved this result further.
Conclusion:
This new PDT drug is an effective PDT sensitizer for MGC803 cells and the death mode of cells is mainly necrosis.
Insights
A novel photodynamic therapeutic (PDT) drug effectively kills MGC803 cancer cells when combined with light. This PDT drug, localized in lysosomes, induces cell death primarily through necrosis, demonstrating its potential as a sensitizer.
Area of Science:
- Biochemistry
- Cell Biology
- Photomedicine
Background:
- Photodynamic therapy (PDT) offers a targeted approach for cancer treatment.
- Developing novel photosensitizers is crucial for enhancing PDT efficacy.
- MGC803 cells represent a relevant model for gastric cancer research.
Purpose of the Study:
- To evaluate the efficacy of a newly synthesized photodynamic therapeutic (PDT) drug against MGC803 cells.
- To elucidate the mechanisms underlying the PDT drug's action, including its photostability, cellular localization, and mode of cell death.
Main Methods:
- Photostability assessed using a bleaching method.
- Cytotoxicity determined by MTT assay post-PDT.
- Subcellular localization investigated via laser scanning confocal microscopy (LSCM).
- Cell death modes analyzed using Hoechst staining and Annexin V/PI flow cytometry.
Main Results:
- The PDT drug exhibited good photostability upon repeated illumination.
- No cytotoxicity observed with the drug or irradiation alone; significant cell killing occurred with the combination (P<0.05).
- Phototoxicity increased with concentration, with an LD50 of 1.74 μmol/L.
- The drug localized within the lysosomes of MGC803 cells.
- Cell death was predominantly necrosis, confirmed by Hoechst staining and Annexin V/PI analysis.
Conclusions:
- The novel PDT drug functions as an effective photosensitizer for MGC803 cells.
- The primary mechanism of cell death induced by this PDT drug is necrosis.
