Chenoufi N, Raoul J L, Lescoat G, Brissot P, Bourguet P
Centre E Marquis, and Institut National de la Santé et de la Recherche Médicale Unité 49, Hôpital Pontchaillou, Rennes, France.
J Nucl Med. 1998 May;39(5):900-3.
Radionuclide therapy is currently used in the treatment of some malignancies, including hepatocellular carcinoma. The effects of external beam radiotherapy are improved by combining it with chemotherapy. The aim of this study was to determine whether such a synergistic effect could be demonstrated in vitro with internal radiation therapy.
HepG2 cells were cultured from Day 0 to Day 8 under the following conditions: exposure for 4 hr on Day 2 to increasing concentrations of 5-fluorouracil (5FU), doxorubicin or cisplatin (CDDP); exposure from Day 2 to Day 8 to increasing concentrations of 131-iodide; exposure on Day 2 to low-toxicity doses of drugs for 4 hr, followed by exposure to 131I at increasing concentrations; and exposure to increasing concentrations of 131I from Day 2 to Day 8, with exposure for 4 hr on Day 6 to the drugs. Cell toxicity was assessed by enzyme release (lactate dehydrogenase and aspartate aminotransferase) in the culture medium and on cell survival (protein and tetrazolium dye test). All cultures were run in triplicate.
A dose- and time-dependent toxicity was demonstrated with doxorubicin and CDDP but not with 5FU. When HepG2 cells were exposed to 131I, the toxicity was rather low, but significant, and was time- and dose-dependent. Treating these cells with combination radiotherapy and chemotherapy resulted in a toxicity that was significantly greater than that with 131I or chemotherapy drugs alone.
The radiosensitivity of HepG2 cells is low; combining a chemotherapeutic drug with a radiotherapeutic agent improves the radiosensitivity in a synergistic fashion. This combination is thus able to strengthen the therapeutic effect of internal radiation therapy in different malignancies, particularly in hepatocellular carcinoma.
放射性核素疗法目前用于治疗某些恶性肿瘤，包括肝细胞癌。外照射放疗与化疗联合使用可提高其疗效。本研究的目的是确定这种协同效应在体内放射治疗中是否能在体外得到证实。
将HepG2细胞在以下条件下从第0天培养至第8天：在第2天暴露于浓度递增的5-氟尿嘧啶（5FU）、阿霉素或顺铂（CDDP）4小时；从第2天至第8天暴露于浓度递增的131碘；在第2天暴露于低毒性剂量的药物4小时，随后暴露于浓度递增的131I；从第2天至第8天暴露于浓度递增的131I，并在第6天暴露于药物4小时。通过测定培养基中的酶释放（乳酸脱氢酶和天冬氨酸转氨酶）以及细胞存活情况（蛋白质和四氮唑染料试验）评估细胞毒性。所有培养均重复三次。
阿霉素和顺铂显示出剂量和时间依赖性毒性，但5FU未显示。当HepG2细胞暴露于131I时，毒性相当低，但很显著，且呈时间和剂量依赖性。联合放疗和化疗处理这些细胞导致的毒性明显大于单独使用131I或化疗药物。
HepG2细胞的放射敏感性较低；化疗药物与放射治疗剂联合使用可协同提高放射敏感性。因此，这种联合能够增强体内放射治疗对不同恶性肿瘤，特别是肝细胞癌的治疗效果。
