Lung cancer has become one of common malignant tumors around the world now, both at home and abroad, and has been increasingly recognized as the “two first”, that is “first incidence” and “first mortality” [[1], [2], [3]]. Lung cancer can be mainly divided into non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), with the worst prognosis being non-small cell lung cancer, accounting for over 80 % [[4], [5], [6]]. Due to the insidious symptoms in early NSCLC patients, most of them are already in the terminal stage when they were diagnosed. And, the tumor develops rapidly with poor prognosis, making it is impossible for patients to undergo operation. Therefore, radiation therapy is the preferred treatment plan [[7], [8], [9], [10]]. However, most advanced lung cancer patients relapse after radiotherapy, and the 5-years survival rate of them is very low [[11], [12], [13]]. Therefore, how to treat patients with radiation resistance and how to select chemotherapy drugs are very important issues for the treatment of lung cancer.

At present, the most commonly used chemotherapy drug after radiotherapy is Cisplatin, which has excellent killing effect on various tumors [[14], [15], [16], [17], [18]] but has also significant side effects, such as nausea, vomiting, hair loss, renal function damage and so on. Not only that, Cisplatin is also highly susceptible to drug resistance [[19], [20], [21], [22]], causing the need of replacing it with other platinum chemotherapy drugs, or using immunotherapy and molecular targeted therapy [23,24]. However, the efficacies of other platinum chemotherapy drugs are lower than that of Cisplatin. On the other hand, immunotherapy and molecular targeted therapy are only effective for specific cancer populations with genetic mutations. Moreover, molecular targeted drugs are expensive, and most families cannot afford the high medical expenses. Therefore, the design and development of new chemotherapy drugs with high efficacy and low price are urgent for saving cancer patients.

In recent years, besides the well-known transition metal ions [[25], [26], [27]], the investigations on anticancer drugs have been expanded to other metal ions, such as rare earth ions. Rare earth ions have many advantages such as small size, low toxicity, long life span, large stokes shift and unique linear emission spectra [28]. Since the discovery of their anticancer activity, more and more investigations on design and utilization of rare earth complexes for tumor treatment have been reported [[29], [30], [31], [32]]. In 2014, Tao Zhang et al. developed a gadolinium porphyrin complex (Gd-N) which can selectively enrich into tumor cells, thereby reducing damage to normal cells and producing singlet oxygen under two-photon excitation to exert cytotoxic effects [33]. This gadolinium porphyrin complex can effectively inhibit tumor growth, indicates that Gd-N can serve as photodynamic therapy agent for the treatment of malignant tumors. In 2017, Yan Zhou et al. synthesized an erbium porphyrin complex and linked it onto a specific peptide chain, targeting integrin αvβ3 overexpression of bladder cancer cells [34]. The ligand porphyrin can produce singlet oxygen and thus inhibit the proliferation of bladder cancer cells, which means that rare earth complexes with porphyrin as ligand are potential chemotherapy drugs. However, to the best of our knowledge, there are still no reports about the application of rare earth complexes in the treatment of radiation resistant tumor cells.

In this study, we focused on the design and application of rare earth complexes in inhibiting radiation resistant tumor cells. Firstly, screening rare earth erbium ions and using biocompatible porphyrins as ligands, the tetraphenylporphyrin erbium acetylacetonate (Er(acac)TPP) was synthesized and purified precisely. Then, experimental data indicate that the obtained Er(acac)TPP has different inhibitory abilities on different NSCLC cells. Especially, we observed the relatively stronger inhibitory effects of Er(acac)TPP on H1299 and A549 cells compared with Cisplatin. On the other hand, Er(acac)TPP also exhibits particularly strong toxicity to A549-RR cells. More importantly, the toxicities of Er(acac)TPP to normal lung epithelial cells and renal tubular cells are very low, indicating that the side effects of Er(acac)TPP will be relatively weaker. Our experimental results confirmed that Er(acac)TPP is a potential chemotherapy drug for NSCLC patients and A549 radiation resistant patients.