Asano Yohei, Han Qinghong, Mizuta Kohei, Kang Byung Mo, Kim Jin Soo, Yamamoto Norio, Hayashi Katsuhiro, Kimura Hiroaki, Miwa Shinji, Igarashi Kentaro, Higuchi Takashi, Morinaga Sei, Tsuchiya Hiroyuki, Demura Satoru, Hoffman Robert M
AntiCancer Inc., San Diego, CA, U.S.A.
Department of Surgery, University of California, San Diego, CA, U.S.A.
Anticancer Res. 2025 May;45(5):1871-1876. doi: 10.21873/anticanres.17566.
BACKGROUND/AIM: Cisplatinum (CDDP) is used as first-line therapy in lung cancer. To further improve the therapeutic efficacy of CDDP, we focused on methionine addiction of cancer, known as the Hoffman effect. The present study aimed to determine the synergistic efficacy of the combination of CDDP and recombinant methioninase (rMETase) to target methionine addiction of lung cancer.
In the present study, we used the Lewis lung carcinoma (LLC) cell line and Hs27 normal human fibroblasts, as a control. Both cell lines were cultured in 96-well plates (1,000 cells/well) overnight at 37°C and treated with CDDP (from 1 μM to 40 μM) or rMETase (from 0.5 U/ml to 8 U/ml) for 72 h. Then, we measured the half-maximal inhibitory concentration (IC) values of CDDP and rMETase for both cell lines using the WST-8 reagent to determine cell viability. We then determined the synergistic efficacy of the combination of CDDP and rMETase at their respective IC concentrations on cell viability for both cell lines.
For LLC cells the IC of CDDP was 0.55 μM and the IC of rMETase was 0.45 U/ml. For Hs27 cells, the IC was 1.21 μM for CDDP and 0.69 U/ml for rMETase. The combination of rMETase and CDDP, at their respective IC concentrations, showed synergistic efficacy on LLC cells, but not on Hs27 cells.
Combination therapy with rMETase and CDDP shows promise for treating lung cancer and may be readily translated to the clinic.
背景/目的：顺铂（CDDP）被用作肺癌的一线治疗药物。为了进一步提高CDDP的治疗效果，我们聚焦于癌症的蛋氨酸成瘾性，即霍夫曼效应。本研究旨在确定CDDP与重组蛋氨酸酶（rMETase）联合使用针对肺癌蛋氨酸成瘾性的协同疗效。
在本研究中，我们使用Lewis肺癌（LLC）细胞系和Hs27正常人成纤维细胞作为对照。两种细胞系均在96孔板中（每孔1000个细胞）于37°C培养过夜，并用CDDP（浓度从1μM至40μM）或rMETase（浓度从0.5 U/ml至8 U/ml）处理72小时。然后，我们使用WST - 8试剂测量CDDP和rMETase对两种细胞系的半数最大抑制浓度（IC）值，以确定细胞活力。接着，我们在各自的IC浓度下确定CDDP和rMETase联合使用对两种细胞系细胞活力的协同疗效。
对于LLC细胞，CDDP的IC为0.55μM，rMETase的IC为0.45 U/ml。对于Hs27细胞，CDDP的IC为1.21μM，rMETase的IC为0.69 U/ml。rMETase和CDDP在各自的IC浓度下联合使用对LLC细胞显示出协同疗效，但对Hs27细胞则没有。
rMETase与CDDP联合治疗在肺癌治疗中显示出前景，并且可能易于转化应用于临床。
