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Chemosensitivity testing of human lung cancer tissues using the succinate dehydrogenase inhibition test
T Mitsudomi1, S Kaneko, M Tateishi
1Department of Surgery II, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Abstract:
We examined the chemosensitivity of 57 primary lung cancer specimens to 9 antitumor drugs, using the succinate dehydrogenase inhibition (SDI) test. Average succinate dehydrogenase (SD) activity was reduced to less than 50% by cis-diaminedichloroplatinum (II) (DDP), cyclophosphamide (CPA), carboquone (CQ), mitomycin C (MMC) and adriamycin (ADM). The lung cancer cells were relatively resistant to pepleomycin (PEP), 5-fluorouracil (5 FU), vincristine (VCR) and vindesine (VDS). Small cell lung cancers, or early stage lung cancers, tended to be more sensitive to these antitumor drugs. However, differences in sensitivity with respect to either histology, staging or degree of differentiation were not statistically significant. Correlation of SD activity between 2 drugs was high among those which inhibit DNA synthesis (DDP, CPA, CQ or MMC), or between VCR and VDS (inhibitor of mitosis), however, the correlation between VDS and CPA, CQ or DDP was weak. The SDI test is a simple in vitro method readily available to aid in selecting drugs to treat patients with lung cancer.
Insights
The succinate dehydrogenase inhibition (SDI) test assessed lung cancer chemosensitivity to nine drugs. Cis-diaminedichloroplatinum (II) and others showed effectiveness, while some drugs were less effective, aiding in drug selection.
Area of Science:
- Oncology
- Pharmacology
- Biochemistry
Background:
- Lung cancer exhibits variable responses to chemotherapy.
- Accurate prediction of drug sensitivity is crucial for effective treatment.
- In vitro chemosensitivity testing can guide therapeutic decisions.
Purpose of the Study:
- To evaluate the chemosensitivity of primary lung cancer specimens using the succinate dehydrogenase inhibition (SDI) test.
- To determine the efficacy of nine different antitumor drugs against lung cancer cells.
- To explore the utility of the SDI test in aiding drug selection for lung cancer patients.
Main Methods:
- The succinate dehydrogenase inhibition (SDI) test was performed on 57 primary lung cancer specimens.
- Chemosensitivity was assessed against nine antitumor drugs, including cis-diaminedichloroplatinum (II) (DDP), cyclophosphamide (CPA), carboquone (CQ), mitomycin C (MMC), adriamycin (ADM), pepleomycin (PEP), 5-fluorouracil (5 FU), vincristine (VCR), and vindesine (VDS).
- Succinate dehydrogenase (SD) activity was measured to determine drug-induced inhibition.
Main Results:
- Average SD activity was reduced by over 50% with DDP, CPA, CQ, MMC, and ADM.
- Lung cancer cells showed relative resistance to PEP, 5 FU, VCR, and VDS.
- Small cell and early-stage lung cancers tended to be more sensitive, though differences were not statistically significant.
- Strong correlations in SD activity were observed between drugs inhibiting DNA synthesis (DDP, CPA, CQ, MMC) and between VCR and VDS, but weak correlations were found between VDS and DNA synthesis inhibitors.
Conclusions:
- The SDI test is a practical in vitro method for assessing lung cancer chemosensitivity.
- Certain drugs like DDP, CPA, CQ, MMC, and ADM demonstrate significant inhibitory effects on lung cancer cells.
- The SDI test can assist clinicians in selecting appropriate chemotherapy regimens for individual lung cancer patients.